Abstract
Various mutations in humans and animals lead to the selective and progressive degeneration of motoneurons, resulting in muscular weakness, subsequent paralysis, and death (1–3). Amyotrophic lateral sclerosis (ALS) is the most common adult human motoneuron disease, but the vast majority of sporadic and familial cases of ALS are still of unknown origin (4). Murine models of motoneuron diseases, derived from spontaneous mutations in the colonies, have been known for half a century. Prior to the first identifications of the mutated proteins in human ALS, they have largely been used to explore the disease etiology. The chromosomal localization of these mutations does not favor a genetic similarity between these murine models and the few human forms of the disease for which the mutation or the chromosomal localization is known. Yet the fact that most human ALS cases are of unknown etiology and the recent discovery of molecules with no known role in motoneuron survival (5–7), indicate that these murine mutants may still contribute to the understanding of motoneuronal degenerative processes. This can be exemplified by the work performed on the wobbler mouse, one of the oldest and most extensively studied models, which is reviewed here.
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Price D.L., Cleveland D.W., and Koliatsos V.E. (1994) Motor neurone disease and animal models. Neurobiol Disease 1, 3–11.
Bruijn L.I. and Cleveland D.W. (1996) Mechanisms of selective motor neuron death in ALS: insights from transgenic mouse models of motor neuron disease. J Neuropathol. Appl. Neurobiol. 22, 373–387.
Brahe C. and Bertini E. (1996) Spinal muscular atrophies: recent insights and impact on molecular diagnosis. J. Mol. Med. 74, 555–562.
Cleveland D.W. and Rothstein J.D. (2001) From Charcot to Lou Gehrig: deciphering selective motor neuron death in ALS. Nat. Rev. Neurosci. 2, 806–819.
Oosthuyse B., Moons L., Storkebaum E., H H.B., Nuyens D., Brusselmans K., Dorpe J.V., et al. (2001) Deletion of the hypoxia-response element in the vascular endothelial growth factor promoter causes motor neuron degeneration. Nat Genet. 28, 131–138.
Yang Y., Hentati A., Deng H.X., Dabbagh O., Sasaki T., Hirano M., et al. (2001) The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis. Nat. Genet. 20, 160–165.
Hadano S., Hand C.K., Osuga H., Yanagisawa Y., Otomo A., Devon R.S., et al. (2001) A gene encoding a putative GTPase regulator is mutated in familial amyotrophic lateral sclerosis 2. Nat. Genet. 29, 166–173.
Falconer D.S. (1956) Mouse News Lett. 15, 23.
Lefebvre S., Bürglen L., Reboullet S., Clermont O., Burlet P., Violet L., et al. (1995) Identification and characterization of a spinal muscular atrophy determining gene. Cell 80, 155–165.
Pioro E.P., Wang Y., Moore J.K., Ng T.C., Trapp B.D., Klinkosz B., et al. (1998) Neuronal pathology in the wobbler mouse brain revealed by in vivo proton magnetic resonance spectroscopy and immunocytochemistry. Neuroreport 9, 3041–3046.
Andrews J.M., Gardner M.B., Wolfgram F.D., Ellison G.W., Porter D.D., and Brandkamp W.W. (1974) Studies on a murin form of spontaneous lower motor neuron degeneration- the wobbler (wr) mouse. Am. J. Pathol. 76, 63–78.
Kaupmann K., Simon-Chazottes D., Guénet J.L., and Jockush H. (1992) Wobbler, a mutation affecting motoneuron survival and gonadal functions in the mouse, maps to proximal chromosome 11. Genomics 13, 39–43.
Korthaus D., Wedemeyer N., Lengeling A., Ronsiek M., Jockusch H., and Schmitt-John T. (1997) Integrated variation hybrid map of human chromosome 2p13: possible involvement of Dynactin in neuromuscular diseases. Genomics 43, 242–244.
Resch K., Korthaus D., Wedemeyer N., Lengeling A., Ronsiek M., Thiel C., et al. (1998) Homology between human chromosome 2p13.3 and the wobbler critical region on mouse chromosome 11: comparative high-resolution mapping of STS and EST loci on YAC/BAC contigs. Mamm. Genome 9, 893–898.
Wedemeyer N., Lengeling A., Ronsiek M., Korthaus D., Baer K., Wuttke M., et al. (1996) YAC contigs of the Rab1 and wobbler (wr) spinal muscular atrophy gene region on proximal mouse chromosome 11 and of the homologous region on human chromosome 2p. Genomics 32, 447–454.
Fuchs S., Resch K., Thiel C., Ulbrich M., Platzer M., Jockusch H., et al. (2002) Comparative transcription map of the wobbler critical region on mouse chromosome 11 and the homologous region on human chromosome 2p13–14. BMC Genet. 3, 14–20.
Nabetani A., I I.H., Morisaki H., Oshimura M., and T T.M. (1997) Mouse U2af1-rs1 is a neomorphic imprinted gene. Mol. Cell. Biol. 17, 789–798.
Cheng S.D., Peng H.L., and Chang H.Y. (1997) Localization of the human UGP2 gene encoding the muscle isoform of UDPglucose pyrophosphorylase to 2p13–p14 by fluorescence in situ hybridization. Genomics 1, 414–416.
Yu K.Y., Kwon H.J., Norman D.A., Vig E., Goebl M.G., and Harrington M.A. (2002) Cutting edge: mouse pellino-2 modulates IL-1 and lipopolysaccharide signaling. J. Immunol. 169, 4075–4078.
Resch K., Jockusch H., and Schmitt-John T. (2001) Assignment of homologous genes, Peli1/PELI1 and Peli2/PELI2, for the Pelle adaptor protein Pellino to mouse chromosomes 11 and 14 and human chromosomes 2p13.3 and 14q21, respectively, by physical and radiation hybrid mapping. Cytogenet. Cell Genet. 92, 172–174.
Boyl P.P., M M.S., Annino A., Barbera J.P., Acampora D., and Simeone A. (2001) Otx genes in the development and evolution of the vertebrate brain. Int. J. Dev. Neurosci. 19, 353–363.
Stenner-Liewen F., Luo G., Sahin U., Tureci O., Koslovski M., Kautz I., et al. (2000) Definition of tumor-associated antigens in hepatocellular carcinoma. Cancer Epidemiol. Biomark. Prev. 9, 285–290.
Korthaus D., Wedemeyer N., Wiegand C., and Jockusch H. (1996) The gene for cytoplasmic malate dehydrogenase, Mor2, is closely linked to the wobbler spinal muscular atrophy gene (wr). Mamm. Genome 7, 250.
Des Portes V., Coulpier M., Melki J., and Dreyfus P.A. (1994) Early detection of mouse wobbler mutation: a model of pathological motoneurone death. Neuroreport 5, 1861–1864.
Ishiyama T., Klinkosz B., Pioro E.P., and Mitsumoto H. (1997) Genetic transfert of the wobbler gene to a C57BL/6J X NZB hybrid stock: natural history of the motor neuron disease and the response to CNTF and BDNF cotreatment. Exp Neurol. 148, 247–255.
Rathke-Hartlieb S., Schmidt V.C., Jockusch H., Schmitt-John T., and Bartsch J.W. (1999) Spatiotemporal progression of neurodegeneration and glia activation in the wobbler neuropathy of the mouse. Neuroreport 10, 3411–3416.
Ulbrich M., Schmidt V.C., Ronsiek M., Mussmann A., Bartsch J.W., Augustin M., et al. (2002) Genetic modifiers that aggravate the neurological phenotype of the wobbler mouse. Neuroreport 13, 535–539.
Leestma J.E. and Sepsenwol S. (1980) Sperm tail axoneme alterations in the wobbler mouse. J. Reprod. Fert. 58, 267–270.
Heimann P., Laage S., and Jockusch H. (1991) Defect of sperm assembly in a neurological mutant of the mouse, wobbler (wr). Differentiation 47, 77–83.
Augustin M., Heimann P., Rathke S., and Jockusch H. (1997) Spinal muscular atrophy gene wobbler of the mouse: evidence from the chimeric spinal cord and testis for cell-autonomous function. Dev. Dyn. 209, 286–295.
Stoppini L., Buchs P.A., and Muller D. (1991) A simple method for organotypic cultures of nervous tissue. J. Neurosci. Methods 37, 173–182.
Dockery P., Tang Y., Morais M., and Vacca-Galloway L.L. (1997) Neuron volume in the ventral horn in wobbler mouse motoneuron disease: a light microscope stereological study. J. Anat. 191, 89–98.
Duchen L.W. and Strich S.J. (1968) An hereditary motor neurone disease with progressive denervation of muscle in the mouse: the mutant wobbler. J. Neurol. Neurosurg. Psychiat. 31, 535–542.
Pollin M.M., McHanwell S., and Slater C.R. (1990) Loss of motor neurons from the median nerve motor nucleus of the mutant mouse wobbler. J. Neurocytol. 19, 29–38.
Rothstein J.D., Jin L., Dykes-Hoberg M., and Kuncl R.W. (1993) Chronic inhibition of glutamate uptake produces a model of slow neurotoxicity. Proc. Natl. Acad. Sci. USA 90, 6591–6595.
Meccariello R., Gobellis G., Berruti G., Junier M.P., Ceriani M., Boillée S., et al. (2002) Mouse sperm cell-specific DnaJ first homologue: an evolutionarily concerved protein for spermiogenesis. Biol. Reprod. 66, 1328–1335.
Berruti G., Perego L., Borgonovo B., and Martegani E. (1998) MSJ-1, a new member of the DNAJ family of proteins, is a male germ cell-specific gene product. Exp. Cell Res. 239, 430–441.
Berruti G. and Martegani E. (2001) Msj-1, a mouse testis-specific dnaj protein, is highly expressed in haploid male germ cells and interacts with the testis-specific heat shock protein hsp70-2. Biol. Reprod. 65, 488–495.
Bose P., Fielding R., Ameis K.M., and Vacca-Galloway L.L. (1998) A novel behavioral method to detect motoneuron disease in wobbler mice aged three to seven days old. Brain Res. 813, 334–342.
Bose P., Fielding R., and Vacca-Galloway L.L. (1999) Effects of assisted feeding on wobbler mouse motoneuron disease and serotoninergic and peptidergic sprouting in the cervical spinal horn. Brain Res. Bull. 48, 429–439.
Coulpier M., Junier M.P., Peschanski M., and Dreyfus P.A. (1996) Bcl-2 sensitivity differenciates two pathways for motoneuronal death in the wobbler mouse. J. Neurosci. 16, 5897–5904.
Smith J.P., Hicks P.M., Ortiz L.R., Martinez M.J., and Mandler R.N. (1995) Quantitative measurement of muscle strength in the mouse. J. Neurosci. Methods 62, 15–19.
Ikeda K. and Mitsumoto H. (1993) In vivo and in vitro muscle tensions in wobbler mouse motor neuron disease. Muscle Nerve 16, 979–981.
Andrews J.M. (1975) The fine structure of the cervical spinal cord, ventral root and brachial nerves in the wobbler (wr) mouse. J. Neuropathol. Exp. Neurol. 34, 12–27.
Blondet B., Carpentier G., Ait-Ikhlef A., Murawsky M., and Rieger F. (2002) Motoneuron morphological alterations before and after the onset of the disease in the wobbler mouse. Brain Res. 930, 53–57.
Mitsumoto H. and Bradley W.G. (1982) Murin motor neuron disease (the wobbler mouse): degeneration and regeneration of the lower motor neuron. Brain 105, 811–834.
Blondet B., Aït-Ikhlef A., Murawsky M., and Rieger F. (2001) Transient DNA fragmentation in nervous system during the early course of a murine neurodegenerative disease. Neurosci. Lett. 305, 202–206.
Carpenter S. (1968) Proximal axonal enlargement in motor neuron disease. Neurology 18, 841–851.
Chou S.M. and Fakadej A.V. (1971) Ultrastructure of chromatolytic motor neurons and anterior spinal roots in a case of Werdnig-Hoffman disease. J. Neuropathol. Exp. Neurol. 30, 368–379.
Hirano A., Donnenfeld H., Sasaki S., and Nakano I. (1984) Fine structural observations of neurofilamentous changes in amyotrophic lateral sclerosis. J. Neuropathol. Exp. Neurol. 43, 461–470.
Hirano A., Nakano I., Kurland L.T., Mulder D.W., Holley P.W., and Saccomanno G. (1984) Fine structural study of neurofibrillary changes in a family with amyotrophic lateral sclerosis. J. Neuropathol. Exp. Neurol. 43, 471–480.
Rouleau G.A., Clark A.W., Rooke K., Pramatorava A., Krizus A., Suchowersky O., et al. (1996) SOD1 mutation is associated with accumulation of neurofilaments in amyotrophic lateral sclerosis. Ann. Neurol. 39, 128–131.
Dal Canto M.C. and Gurney M.E. (1994) Development of central nervous system pathology in murine transgenic model of human amyotrophic lateral sclerosis. Am. J. Pathol. 145, 1271–1279.
Dal Canto M.C. and Gurney M.E. (1995) Neuropathological changes in two lines of mice carrying a transgene for mutant human Cu,Zn SOD, and in mice overexpressing wild type human SOD: a model of familial amyotrophic lateral sclerosis (FALS). Brain Res. 676, 25–40.
Dal Canto M.C. and Gurney M.E. (1997) A low expressor line of transgenic mice carrying a mutant human Cu,Zn superoxide dismutase (SOD1)gene develops pathological changes that most closely ressemble those in human amyotrophic lateral sclerosis. Acta Neuropathol. 93, 537–550.
Tu P.-H., Raju P., Robinson K.A., Gurney M.E., Trojanowski J.Q., and Lee V.M.-Y. (1996) Transgenic mice carrying a human mutant superoxide dismutase transgene develop neuronal cytoskeletal pathology ressembling human amyotrophic lateral sclerosis lesions. Proc. Natl. Acad. Sci. USA 93, 3155–3160.
Callahan L.M., Wylen E.L., Messer A., and Mazurkiewicz J.E. (1991) Neurofilament distribution is altered in the mnd (motor neuron degeneration) mouse. J. Neuropathol. Exp. Neurol. 50, 491–504.
Al-Chalabi A., Andersen P.M., Nilsson P., Chioza B., Andersson J.L., Russ C., et al. (1999) Deletions of the heavy neurofilament subunit tail in amyotrophic lateral sclerosis. Hum. Mol. Genet. 8, 157–164.
Pernas-Alonso R., Schaffner A.E., Perrone-Capano C., Orlando A., Morelli F., Hansen C.T., et al. (1996) Early upregulation of medium neurofilament gene expression in developing spinal cord of the wobbler mouse mutant. Brain Res. Mol. Brain Res. 38, 267–275.
Pernas-Alonso R., Perrone-Capano C., Volpicelli F., and Porzio U.D. (2001) Regionalized neurofilament accumulation and motoneuron degeneration are linked phenotypes in wobbler neuromuscular disease. Neurobiol. Dis. 8, 581–589.
Williamson T.L., Bruijn L.I., Zhu Q., Anderson K.L., Anderson S.D., Julien J.-P., et al. (1998) Absence of neurofilaments reduces the selective vulnerability of motor neurons and slows disease caused by a familial amyotrophic lateral sclerosis-linked superoxyde dismutase 1 mutant. Proc. Natl. Acad. Sci. USA 95, 9631–9636.
Morrison B.M., Shu I.-W., Wilcox A.L., Gordon J.W., and Morrison J.H. (2000) Early and selective pathology of light chain neurofilament in the spinal cord and sciatic nerve of G86R mutant superoxide dismutase transgenic mice. Exp. Neurol. 165, 207–220.
Kong J. and Xu Z. (2000) Overexpression of neurofilament subunit NF-L and NF-H extends survival of a mouse model for amyotrophic lateral sclerosis. Neurosci. Lett. 281, 72–74.
Coté F., Collard J.F. and Julien J.P. (1993) Progressive neuronopathy in transgenic mice expressing the human neurofilament heavy gene: a mouse model of amyotrophic lateral sclerosis. Cell 73, 35–46.
Xu Z., Cork L.C., Griffin J.W., and Cleveland D.W. (1993) Increased expression of neurofilament subunit NF-L produces morphological alterations that resemble the pathology of human motor neuron disease. Cell 73, 23–33.
Julien J.P. (1997) Neurofilaments and motor neurone disease. Trends Cell Biol. 7, 243–249.
Braak H. and Braak E. (2000) Pathoanatomy of parkinson’s disease. J. Neurol. 247, II3-II10.
Ince P.G., Lowe J., and Shaw P.J. (1998) Amyotrophic lateral sclerosis: current issues in classification, pathogenesisi and molecular pathology. Neuropathol. Appl. Neurobiol. 24, 104–107.
Ince P.G., Tomkins J., Slade J.Y., Thatcher N.M., and Shaw P.J. (1998) Amyotrophic lateral sclerosis associated with genetic abnormalities in the gene encoding Cu/Zn superoxide dismutase: molecular pathology of five new cases, and comparison with previous reports and 73 sporadic cases of ALS. J Neuropathol. Exp. Neurol. 57, 895–904.
Lansbury Jr P.T. and Kosik K.S. (2000) Neurodegeneration: new clues on inclusions. Chem. Biol. 7, R9-R12.
Sieradzan K.A. and Mann D.M. (2001) The selective vulnerability of nerve cells in Huntington’s disease. Neuropathol. Appl. Neurobiol. 27, 1–21.
Welch W.J. and Gambetti P. (1998) Chaperoning brain diseases. Nature 392, 23–24.
Paulson H.L. (1999) Protein fate in neurodegenerative proteinopathies: polyglutamine diseases join (mis)fold. Am. J. Hum. Genet. 64, 339–345.
Sherman M.Y. and Goldberg A.L. (2001) Cellular defenses against unfolded proteins: a cell biologist thinks about neurodegenerative diseases. Neuron 29, 15–32.
Bercovich B., Stankovski I., Mayer A., Blumenfeld N., Laszlo A., Schwartz A.L., et al. (1997) Ubiquitin-dependant degradation of certain protein substrates in vitro requires the molecular chaperone Hsc70. J. Biol. Chem. 272, 9002–9010.
Cutforth T. and Rubin G.M. (1994) Mutations in Hsp83 and cdc37 impair signaling by the sevenless receptor tyrosine kinasa in Drosophila. Cell 77, 1027–1036.
Cyr D.M., Langer T., and Douglas M.G. (1994) DnaJ-like proteins: molecular chaperones and specific regulators of Hsp70. Trends Biol. Sci. 19, 176–181.
Hayes S.A. and Dice J.F. (1996) Roles of molecular chaperones in protein degradation. J. Cell Biol. 132, 255–258.
Kimura Y., Yahara I., and Lindquist S. (1995) Role of the protein chaperone YDJ1 in establishing Hsp90-mediated signal transduction pathways. Science 268, 1362–1365.
Wigley W.C., Fabunmi R.P., Lee M.G., Marino C.R., Muallem S., DeMartino G.N., and Thomas P.J. (1999) Dynamic association of proteasomal machinery with centrosome. J Cell Biol. 145, 481–490.
Cummings C.J., Mancini M.A., Antalffy B., DeFranco D.B., Orr H.T., and Zoghbi H.Y. (1998) Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in SCA1. Nat. Genet. 19, 148–154.
Chai Y., Koppenhafer S.L., Bonini N.M., and Paulson H.L. (1999) Analysis of the role of heat shock protein (Hsp) molecular chaperones in polyglutamine disease. J. Neurosci. 19, 10,338–10,347.
Bruening W., Roy J., Giasson B., Figlewicz D.A., Mushynski W.E., and Durham H.D. (1999) Up-regulation of protein chaperones preserves viability of cells expressing toxic Cu/Zn-superoxide dismutase mutants associated with amyotrophic lateral sclerosis. J. Neurochem. 72, 693–699.
Stenoien D.L., Cummings C.J., Adams H.P., Mancini M.G., Patel K., DeMartino G.N., et al. (1999) Polyglutamine-expanded androgen receptors forms aggregates that sequester heat shock proteins, proteasome components and SRC-1, and are suppressed by HDJ-2 chaperone. Hum. Mol. Genet. 8, 731–741.
Warrick J.M., Chan H.Y.E., Gray-Board G.L., Chai Y., Paulson H.L., and Bonini N.M. (1999) Supression of polyglutamine-mediated neurodegeneration in Drosophila by the molecular chaperone HSP70. Nat. Genet. 23, 425–428.
Jana N.R., Tanaka M., Wang G.H., and Nukina N. (2000) Polyglutamine length-dependent interaction of Hsp40 and Hsp70 family chaperones with truncated N-terminal huntingtin: their role in suppression of aggregation and cellular toxicity. Hum. Mol. Genet. 9, 2009–2018.
Kobayashi Y., Kume A., Li M., Doyu M., Hata M., Ohtsuka K., et al. (2000) Chaperones Hsp70 and Hsp40 suppress aggregate formation and apoptosis in cultured neuronal cell expressing truncated androgen receptor protein with expanded polyglutamine tract. J. Biol. Chem. 275, 8772–8778.
Shinder G.A., Lacourse M.C., Minotti S., and Durham H.D. (2001) Mutant Cu/Zn- superoxide dismutase proteins have altered solubility and interact with heat shock/stress proteins in models of amyotrophic lateral sclerosis. J. Biol. Chem. 276, 12,791–12,796.
Lee D.H., Sherman M.Y., and Goldberg A.L. (1996) Involvement of the molecular chaperone Ydj1 in the ubiquitin-dependent degradation of short-lived and abnormal proteins in Saccharomyces cerevisiae. Mol. Cell Biol. 16, 4773–4781.
Ohba M. (1997) Modulation of intracellular protein degradation by SSB1-SIS1 chaperon system in yeast S. cerevisiae. FEBS Lett. 409, 307–311.
Pioro E.P., Ishiyama T., Klinkosz B., et al. (1996) Soc. Neurosci. Abstr. 22, 1942.
Boillée S., Berruti G., Meccariello R., Grannec G., Razan F., Pierantoni R., et al. (2002) Early defect in the expression of mouse sperm DnaJ 1, a member of the DNAJ/heat shock protein 40 chaperone protein family, in the spinal cord of the wobbler mouse, a murine model of motoneuronal degeneration. Neuroscience 113, 825–835.
Pieri I., Cifuentes-Diaz C., Oudinet J.P., Blondet B., Rieger F., Gonin S., et al. (2001) Modulation of HSP25 expression during anterior horn motor neuron degeneration in the paralyse mouse mutant. J Neurosci. Res. 65, 247–253.
Junier M.P., Legendre P., Esguerra C.V., Tinel M., Coulpier M., Dreyfus P.A., et al. (1998) Regulation of growth factor gene expression in degenerating motoneurons of the murine mutant wobbler: a cellular patch-sampling/RT-PCR study. Mol. Cell Neurosci. 12, 168–177.
Tsuzaka K., Ishiyama T., Pioro E.P., and Mitsumoto H. (2001) Role of brain-derived neurotrophic factor in wobbler mouse motor neuron disease. Muscle Nerve 24, 474–480.
Junier M., Coulpier M., Forestier N.L., Cadusseau J., Suzuki F., Peschanski M., et al. (1994) Transforming Growth Factor α (TGFα) expression in degenerating motoneurons of the murine mutant wobbler: a neuronal signal for astrogliosis? J. Neurosci. 14, 4206–4216.
Henderson C.E., Camu W., Mettling C., Gouin A., Poulsen K., Karihaloo M., et al. (1993) Neurotrophins promote motor neuron survival and are present in embryonic limb bud. Nature 363, 266–270.
Koliatsos V.E., Clatterbuck R.E., Winslow J.W., Cayouette M.H., and Price D.L. (1993) Evidence that brain-derived neurotrophic factor is a trophic factor for motor neurons in vivo. Neuron 10, 359–367.
Friedman B., Kleinfeld D., Ip N.Y., Verge V.M.K., Moulton R., Boland P., et al. (1995) BDNF and NT-4/5 neurotrophic influences on injured adult spinal motor neuron. J. Neurosci. 15, 1044–1056.
Junier M.P. (2000) What role(s) for the TGFα in the central nervous system? Prog. Neurobiol. 62, 443–473.
Rabchevsky A.G., Weinitz J.M., Coulpier M., Fages C., Tinel M., and Junier M.P. (1998) A role for transforming growth factor alpha as an inducer of astrogliosis. J. Neurosci. 18, 10,541–10,552.
Boillée S., Cadusseau J., Couplier M., Grannec G., and Junier M.P. (2001) Transforming growth factor α: a promoter of motoneuron survival of potential biological relevance. J. Neurosci. 21, 7079–7088.
Lisovoski F., Blot S., Lacombe J.P., Dreyfus P.A., and Junier M.P. (1997) Transforming growth factor alpha expression as a response of murine motor neurons to axonal injury and mutation-induced degeneration. J. Neuropathol. Exp. Neurol. 56, 459–471.
Kobayashi N.R., Bedard A.M., Hincke M.T., and Tetzlaff W. (1996) Increased expression of BDNF and trkB mRNA in rat facial motoneurons after axotomy. Eu. J. Neurosci. 8, 1018–1029.
Kou S.Y., Chiu A.Y., and Patterson P.H. (1995) Differential regulation of motor neuron survival and choline acetyltransferase expression following axotomy. J. Neurobiol. 27, 561–572.
Lowrie M.B. and Vrbova G. (1992) Dependence of postnatal motoneurones on their targets: review and hypothesis. Trends Neurosci. 15, 80–84.
Schlomann U., Rathke-Hartlieb S., Yamamoto S., Jockusch H., and Bartsch J.W. (2000) Tumor Necrosis Factor α induces a metalloprotease-Disintegrin, ADAM8 (CD 156): implications for neuron-glia interactions during neurodegeneration. J. Neurosci. 20, 7964–7971.
Pernas-Alonso R., Schaffner A.E., Hansen C.T., Barker J.L., and Porzio U.d. (1995) Acetylcholine esterase and peripherin mRNA level decrease in wobbler mouse. Neuroreport 6, 597–600.
Popper P., Farber D.B., Micevych P.E., Minoofar K., and Bronstein J.M. (1997) TRPM-2 expression and Tunel staining in neurodegenerative disease: studies in the wobbler and rd mice. Exp. Neurol. 143, 246–254.
Gonzalez Deniselle M.C., Gonzales S.L., Lima A.E., Wilkin G., and Nicola A.F.D. (1999) The 21-aminosteroid U-74389F attenuates hyperexpression of GAP-43 and NAPDH-diaphorase in the spinal cord of wobbler mouse, a model for amyotrophic lateral scerosis. Neurochem. Res. 24, 1–8.
Gonzalez Deniselle M.C., Grillo C.A., Gonzalez S., Roig P., and Nicola A.F.D. (1999) Evidence for down-regulation of GAP-43 mRNA in wobbler mouse spinal motoneurons by corticosterone and a 21-aminosteroid. Brain Res. 841, 78–84.
Clowry G.L. and mcHanwell S. (1996) Expression of nitric oxide synthase by motor neurones in the spinal cord of the mutant mouse wobbler. Neurosci. Lett. 215, 177–180.
Salcedo R.M., Festoff B.W., and Citron B.A. (1998) Quantitative Reverse Transcriptase PCR to gauge increased protease-activated receptor 1 (PAR-1) mRNA copy numbers in the wobbler mutant mouse. J. Mol. Neurosci. 10, 113–119.
Turgeon V.L., Lloyd E.D., Wang S., Festoff B.W., and Houenou L.J. (1998) Thrombin perturbs neurite outgrowth and induces apoptotic cell death in enriched chick spinal motoneuron cultures through caspase activation. J. Neurosci. 18, 6882–6891.
Festoff B.W., D’Andrea M.R., Citron B.A., Rm R.M.S., Smirnova I.V., and Andrade-Gordon P. (2000) Motor neuron cell death in wobbler mutant mice follows overexpression of the G-protein-coupled, protease-activated receptor for thrombin. Mol. Med. 6, 410–429.
Murakami T., Mastaglia F.L., and Bradley W.G. (1980) Reduced protein synthesis in the spinal anterior horn neurons in wobbler mouse mutant. Exp. Neurol. 67, 423–432.
Murakami T., Mastaglia F.L., Mann D.M.A., and Bradley W.G. (1981) Abnormal RNA metabolism in spinal motor neurons in the wobbler mouse. Muscle Nerve 4, 407–412.
Brooks B.R., Lust W.D., Andrews J.M., and Engel W.K. (1978) Decreased spinal cord cGMP in murin (wobbler) spontaneous lower motor neuron degeneration. Arch. Neurol. 35, 590–591.
Krieger C., Perry T.L., Hansen S., and Honoré T. (1991) The wobbler mouse: amino acid contents in brain and spinal cord. Brain Res. 551, 142–144.
Hirsch H.E., Andrews J.M., and Parks M.E. (1974) Acid hydrolases and other enzymes in secondary demyelination: a quantitative histochemical study in the wobbler mouse. J. Neurochem. 23, 935–941.
Court J.A., McDermott J.R., Gibson A.M., Marshall E., Bloxham C.A., Perry R.H., et al. (1987) Raised Thyrotropin-Releasing Hormone, pyroglutamyl aminopeptidase, and proline endopeptidase are present in the spinal cord of wobbler mice but not in human motor neurone disease. J. Neurochem. 49, 1084–1090.
Chelmicka-Schorr E., Sportiello M., Antel J.P., and Arnason B.G.W. (1982) Acid protease activity in spinal cord and muscle in wobbler mouse. J. Neurol. Sci. 56, 141–145.
Gonzalez Deniselle M.C., Gonzalez S., Piroli G., Ferrini M., Lima A.E., and Nicola A.F.D. (1997) Glucocorticoid receptors and actions in the spinal cord of the wobbler mouse, a model for neurodegenerative disease. J. Steroid Biochem. Mol. Biol. 60, 205–213.
Yung K.K.L., Tang F., Fielding R., Du Y.H., and Vacca-Galloway L.L. (1992) Alteration in the levels of thyrotropin releasing hormone, substance P and enkephalins in the spinal cord, brainstem, hypothalamus and midbrain of the wobbler mouse at different stages of the motoneuron disease. Neuroscience 50, 209–222.
Yung K.K.L., Tang F., and Vacca-Galloway L.L. (1994) Alterations in acetylcholinesterase and choline acetyltransferase activities and neuropeptide levels in the ventral spinal cord of the wobbler mouse during inherited motoneuron disease. Brain Res. 638, 337–342.
Tang F., Cheung A. and Vacca-Galloway L.L. (1990) Measurement of neuropeptides in the brain and spinal cord of wobbler mouse: a model for motoneuron disease. Brain Res. 518, 329–333.
Yung K.K.L., Tang F., and Vacca-Galloway L.L. (1992) Decrease of enkephalins in cerebellum during wobbler mouse motoneuron disease. Brain Res. 599, 175–180.
Deng Y.P., Li X.S., Zhang S.H., and Vacca-Galloway L.L. (1996) Changes in receptor levels from thyrotropin releasing hormone, serotonin, and substance P in cervical spinal cord of wobbler mouse: a quantitative autoradiography study during early and late stages of the motoneuron disease. Brain Res. 725, 49–60.
Tomiyama M., Kannari K., Nunomura J., Oyama Y., Takebe K., and Matsunaga M. (1994) Quantitative autoradiographic distribution of glutamate receptors in the cervical segment of the spinal cord of wobbler mouse. Brain Res. 650, 353–357.
Blondet B., Barlovatz-Meimon G., Festoff B.W., Soria C., Soria J., Rieger F., et al. (1992) Plasminogen activators in the neuromuscular system of the wobbler mutant mouse. Brain Res. 580, 303–310.
Shi J. and Vacca-Galloway L.L. (1993) Thyrotropin-releasing hormone (TRH) neurons sprout in cervical spinal cord of wobbler mouse. Brain Res. 626, 83–89.
Zhang Y.Q. and Vacca-Galloway L.L. (1992) Decreased immunoreactive (IR) calcitonin gene-related peptide correlates with sprouting of IR-peptidergic and serotoninergic neuronal processes in spinal cord and brain nuclei from the wobbler mouse during motoneuron disease. Brain Res. 587, 169–177.
Shultz L.D., Sweet H.O., Davisson M.T., and Coman D.R. (1982) “Wasted”, a new mutant of the mouse with abnormalities characteristic of ataxia telangiectasia. Nature 297, 402–404.
Chambers D.M., Peters J., and Abbott C.M. (1998) The lethal mutation of the mouse wasted (wst) is a deletion that abolishes expression of a tissue-specific isoform of translation elongation factor 1alpha, encoded by the Eef1a2 gene. Proc. Natl. Acad. Sci. USA 95, 4463–4468.
Gilmore E.C., Nowakowski R.S., Caviness V.S.J., and Herrup K. (2000) Cell birth, cell death, cell diversity and DNA breaks: how do they all fit togather? Trends Neurosci. 23, 100–105.
Bird M.T., Jr E.S., Koestner A., and Reinglass J. (1971) The wobbler mouse mutant: an animal model of hereditary motor system disease. Acta Neuropathol. (Berl). 19, 39–50.
Scidmore M.A., Okamura H.H., and Rose M.D. (1993) Genetic interactions between KAR2 and SEC63, encoding eukaryotic homologues of DnaK and DnaJ in the endoplasmic reticulum. Mol. Biol. Cell 4, 1145–1159.
Sanders S.L., Whitfield K.M., Vogel J.P., Rose M.D., and Schekman R.W. (1992) Sec61p and BIP directly facilitate polypeptide translocation into the ER. Cell 69, 353–365.
Oda K., Wada I., Takami N., Fujiwara T., Misumi Y., and Ikehara Y. (1996) Bip/GRP78 but not calnexin associates with a precursor of glycosylphosphatidylinositol- anchored protein. Biochem. J. 316, 623–630.
Blot S., Poirier C., and Dreyfus P.A. (1995) The mouse mutation muscle deficient (mdf) is characterized by a progressive motoneuron disease. J. Neuropathol. Exp. Neurol. 54, 812–825.
Woloschak G.E., Rodriguez M., and Krco C.J. (1987) Characterization of immunologic and neuropathologic abnormalities in wasted mice. J. Immunol. 138, 2493–2499.
Mitsumoto H., McQuarrie I.G., Kurahashi K., and Sunohara N. (1990) Histometric characteristics and regenerative capacity in wobbler mouse motor neuron disease. Brain 113, 497–507.
La Vail J.H., Koo E.H., and Dekker N.P. (1987) Motoneuron loss in the abducens nucleus of wobbler mice. Brain Res. 404, 127–132.
Biscoe T.J. and Lewkowicz S.J. (1982) Quantitative light and electron microscopic studies on the ventral roots of the wobbler mutant mouse. Q. J. Exp. Physiol. 67, 543–555.
Lewkowicz S.J. (1979) Studies on the localization of the lesion in the wobbler mutant mouse. J. Physiol. (Lond). 289, 39P.
Mitsumoto H. and Gambetti P. (1986) Impaired slow axonal transport in wobbler mouse motor neuron disease. Ann Neurol. 19, 36–43.
Mitsumoto H., Kurahashi K., Jacob J.M., and McQuarrie I.G. (1993) Retardation of fast axonal transport in wobbler mice. Muscle Nerve 16, 542–547.
Mitsumoto H., Ferut A.L., Kurahashi K., and McQuarrie I.G. (1990) Impairment of retrograde axonal transport in wobbler mouse motor neuron disease. Muscle Nerve 13, 121–126.
Mitsumoto H. (1985) Axonal regeneration in wobbler motor neuron disease: quantitative histologic and axonal transport studies. Muscle Nerve 8, 44–51.
Mitsumoto H. and Boggs A.L. (1987) Vacuolated anterior horn cells in wobbler mouse motor neuron disease: peripheral axons and regenerative capacity. J. Neuropathol. Exp. Neurol. 46, 214–222.
Ma W. and Vacca-Galloway L.L. (1992) Spiny interneurons identified in the normal mouse spinal cord show alteration in the wobbler mouse: a model for inherited motoneuron disease. Restorative Neurology and Neuroscience 4, 381–392.
Campbell M.J. (1971) Ultrastructural observations on the wobbler mouse. J. Neuropathol. Exp. Neurol. 31, 190.
Leigh P.N. and Swash M. (1991) Cytoskeletal pathology in motor neuron disease. Adv. Neurol. 56, 115–124.
Lowe J., Mayer R.J., and Landon M. (1993) Ubiquitin in neurodegenerative diseases. Brain Pathol. 3, 55–65.
Kuan C.-Y., Roth K.A., Flavell R.A., and Rakic P. (2000) Mechanisms of programed cell death in the developping brain. Trends Neurosci. 23, 291–297.
Merry D.E. and Korsmeyer S.J. (1997) Bcl-2 gene family in the nervous system. Annu. Rev. Neurosci. 20, 245–267.
Cory S. and Adams J.M. (2002) The Bcl2 family: regulators of the cellular life-or-death switch. Nat. Rev. Cancer 2, 647–656.
Martinou J.C., Dubois-Dauphin M., Staple J.K., Rodriguez I., Frankowski H., Missotten M., et al. (1994) Overexpression of BCL-2 in transgenic mice protects neurons from naturally occurring cell death and experimental ischemia. Neuron 13, 1017–1030.
Aït-Ikhlef A., Murawsky M., Blondet B., Hantaz-Ambroise D., Martinou J.C., and Rieger F. (1995) The motoneuron degeneration in the wobbler mouse is independent of the overexpression of a Bcl2 transgene in neurons. Neurosci. Lett. 199, 163–166.
Gehrmann J., Schoen S.W., and Kreutzberg G.W. (1991) Lesion of the rat entorhinal cortex leads to rapid microglial reaction in the dentate gyrus. A light and electron microscopical study. Acta Neuropathol. 82, 442–455.
Gehrmann J., Gehrmann B.B.R., Gehrmann C.W., Gehrmann A.H.K., and Gehrmann W.K.G. (1995) Reactive microglia in cerebral ischaemia: an early mediator of tissue damage? Neuropathol. Appl. Neurobiol. 21, 277–289.
Chu-Wang I.W. and Oppenheim R.W. (1978) Cell death of motoneurons in the chick spinal cord. J. Comp. Neurol. 177, 33–58.
Pilar G. and Landmesser L. (1976) Ultrastructural differences during embryonic cell death in normal and peripherally deprived ciliary ganglia. J. Cell Biol. 68, 339–356.
Clarke P.G.H. (1990) Developmental cell death: morphological diversity and multiple mechanisms. Anat. Embryol. 181, 195–213.
Oppenheim R.W., Flavell R.A., Vinsant S., Prevette D., Kuan C.-Y., and Rakic P. (2001) Programmed cell death of developping mammalian neurons after genetic deletion of caspases. J. Neurosci. 21, 4752–4760.
Boillée S., Viala L., Peschanski M., and Dreyfus P.A. (2001) Differential microglial response to progressive neurodegeneration in the murine mutant wobbler. Glia 33, 277–287.
Benowitz L.I. and Routtenberg A. (1997) GAP-43: an intrinsic determinant of neuronal development and plasticity. Trends Neurosci. 20, 84–91.
Melki J., Blondet B., Pinçon-Raymond M., Dreyfus P., and Rieger F. (1991) Generalized molecular defects of the neuromuscular junction in skeletal muscle of the wobbler mutant mouse. Neurochem. Int. 18, 425–433.
Reiter R.J. (1995) Oxidative processes and antioxidative defense mechanisms in the aging brain. FASEB J. 9, 526–533.
Liu P.K., Robertson C.S., and Valadka A. (2002) The association between neuronal nitric oxide synthase and neuronal sensitivity in the brain after brain injury. Ann. NY Acad. Sci. 962, 226–241.
Beal M.F., Ferrante R.J., Browne S.E., Matthews R.T., Kowall N.W., and Brown R.H. Jr (1997) Increased 3-nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis. Ann. Neurol. 42, 646–654.
Brown R.H.J. (1995) Superoxide dismutase in familial amyotrophic lateral sclerosis: models for gain of function. Curr. Opin. Neurobiol. 5, 841–846.
Bowling A., Schulz J.B., Brown R.H.J., and Beal M.F. (1993) Superoxide dismutase activity, oxidative damage, and mitochondrial energy metabolism in familial and sporadic amyotrophic lateral sclerosis. J. Neurochem. 61, 2322–2325.
Moore P.K. and Handy R.L. (1997) Selective inhibitors of neuronal nitric oxide synthase—is no NOS really good NOS for the nervous system? Trends Pharmacol. Sci. 18, 204–211.
Clowry G.J. (1993) Axotomy induces NAPDH diaphorase activity in neonatal but not adult motoneurones. Neuroreport 5, 361–364.
Wu W. (1993) Expression of nitric oxide synthase (NOS) in injured CNS neurons as shown by histochemistry for NAPDH-diaphorase. Exp. Neurol. 120, 1–7.
Wu Y., Li Y., Liu H., and Wu W. (1995) Induction of nitric oxide synthase and motoneuron death in newborn and early postnatal rats following spinal root avulsion. Neurosci. Lett. 194, 109–112.
Wu W. and Li L. (1993) Inhibition of nitric oxide synthase reduces motoneuron death due to spinal root avulsion. Neurosci. Lett. 153, 121–124.
Wu W., Han K., Li L., and Schinco F.P. (1994) Implantation of PNS graft inhibits the induction of neuronal nitric oxide synthase and enhances the survival of spinal motoneurons following root avulsion. Exp. Neurol. 129, 335–339.
Wu W., Liuzzi F.J., Schinco F.P., Depto A.S., Li Y., Mong J.A., et al. (1994) Neuronal nitric oxide synthase is induced in spinal neurons by traumatic injury. Neuroscience, 61, 719–726.
Ikeda K., Iwasaki Y., and Kinoshita M. (1998) Neuronal nitric oxide synthase inhibitor, 7-nitroindazole, delays motor dysfunction and spinal motoneuron degeneration in the wobbler mouse. J. Neurol. Sci. 160, 9–15.
Ikeda K., Kinoshita M., Iwasaki Y., Tagaya N., and Shiojima T. (1995) Lecithinized superoxide dismutase retards wobbler mouse motoneuron disease. Neuromusc. Disord. 5, 383–390.
Henderson J.T., Javaheri M., Kopko S., and Roder J.C. (1996) Reduction of lower motor neuron degeneration in wobbler mice by N-Acetyl-L-Cysteine. J. Neurosci. 16, 7574–7582.
Eddleston M. and Mucke L. (1993) Molecular profile of reactive astrocytes—implications for their role in neurologic disease. Neuroscience 54, 15–36.
Ridet J.L., Malhotra S.K., Privat A., and Gage F.H. (1997) Reactive astrocytes: cellular and molecular cues to biological function. Trends. Neurosci. 20, 570–577.
Marty S., Dusart I., and Peschanski M. (1991) Glial changes following an excitotoxic lesion in the CNS — I. Microglia/macrophages. Neuroscience 45, 529–539.
Norenberg M.D. (1994) Astrocyte responses to CNS injury. J. Neuropathol. Exp. Neurol. 53, 213–220.
Streit W.J., Walter S.A., and Pennell N.A. (1999) Reactive microgliosis. Prog. Neurobiol. 57, 563–581.
Laage S., Zobel G., and Jockusch H. (1988) Astrocyte overgrowth in the brain stem and spinal cord of mice affected by spinal atrophy, wobbler. Dev. Neurosci. 10, 190–198.
Hantaz-Ambroise D., Blondet B., Murawsky M., and Rieger F. (1994) Abnormal astrocyte differentiation and defective cellular interactions in wobbler mouse spinal cord. J. Neurocytol. 23, 179–192.
Dahl D. and Bigmani A. (1974) Heterogeneity of the glial fibrillary acidic protein in gliosed human brains. J. Neurol. Sci. 23, 551–563.
Bignami A. and Dahl D. (1976) The astroglial response to stabbing. Immunofluorescence studies with antibodies to astrocyte-specific protein (GFAP) in mammalian and submammalian vertebrates. Neuropathol. Appl. Neurobiol. 2, 99–111.
Eng L.F. (1988) Regulation of glial intermediate filaments in astrogliosis. In The Biochemical Pathology of Astrocytes (Norenberg M.D., Hertz L., and Schousboe A., eds.), Alan R. Liss, New York, NY, pp. 79–90.
Mesulam M.M. (1978) Tetrametyl benzidine for horseradish peroxidase neurohistochemistry: a non-carcinogenic blue reaction product with superior sensitivity for visualizing neural afferents and efferents. J. Histochem. Cytochem. 26, 106–117.
Aït-Ikhlef A., Hantaz-Ambroise D., Jacque C., Belkadi L., and Rieger F. (1999) Astrocyte proliferation induced by wobbler astrocyte conditioned medium is blocked by Tumor Necrosis Factor-α (TNF-α) and interleukin-1β (IL-1β) neutralizing antibodies in vitro. Cell Mol. Biol. 45, 393–400.
Lukes A., Mun-Bryce S., Mun-Bryce M.L., and Mun-Bryce G.A.R. (1999) Extracellular matrix degradation by metalloproteinases and central nervous system diseases. Mol. Neurobiol. 19, 267–284.
Rathke-Hartlieb S., Budde P., Ewert S., Schlomann U., Staege M.S., Jockusch H., et al. (2000) Elevated expression of membrane type 1 metalloproteinase (MT1-MMP) in reactive astrocytes following neurodegeneration in mouse central nervous system. FEBS Lett. 481, 227–234.
Rothstein J.D. (1996) Excitotoxicity hypothesis. Neurology 47, S19-S25.
Choi D.W. (1992) Excitotoxic cell death. J. Neurobiol. 23, 1261–1276.
Blondet B., Hantaz-Ambroise D., Aït-Ikhlief A., Cambier D., Murawsky M., and Rieger F. (1995) Astrocytosis in wobbler mouse spinal cord involves a population of astrocytes which is glutamine synthetase-negative. Neurosci. Lett. 183, 179–182.
Bigini P., Bastone A., and Mennini T. (2001) Glutamate transporters in the spinal cord of the wobbler mouse. Neuroreport 12, 1815–1820.
Gonzalez Deniselle M.C., Lavista-Llanos S., Ferrini M.G., Lima A.E., Roldan A.G., and Nicola A.F.D. (1999) In vitro differences between astrocytes of control and wobbler mice spinal cord. Neurochem. Res. 24, 1535–1541.
Aït-Ikhlef A., Hantaz-Ambroise D., Henderson C.E., and Rieger F. (2000) Influence of factors secreted by wobbler astrocytes on neuronal and motoneuronal survival. J. Neurosci. Res. 59, 100–106.
Pramatarova A., Laganiere J., Roussel J., Brisebois K., and Rouleau G.A. (2001) Neuron-specific expression of mutant superoxide dismutase 1 in transgenic mice does not lead to motor impairment. J. Neurosci. 21, 3369–3374.
Gong Y.H., Parsadanian A.S., Andreeva A., Snider W.D., and Elliott J.L. (2000) Restricted expression of G86R Cu/Zn superoxide dismutase in astrocytes results in astrocytosis but does not cause motoneuron degeneration. J. Neurosci. 20, 660–665.
Zhu Y., Romero M.I., Ghosh P., Ye Z., Charnay P., Rushing E.J., et al. (2001) ablation of NF1 function in neurons induces abnormal development of cerebral cortex and reactive gliosis in the brain. Genes Dev. 15, 859–876.
Kalla R., Liu Z., Xu S., Koppius A., Imai Y., Kloss C.U.A., et al. (2001) Microglia and the early phase of immune surveillance in the axotomized facial motor nucleus: impaired microglial activation and lymphocyte recruitment but no effect on neuronal survival or axonal regeneration in macrophage-colony stimulating factor-deficient mice. J. Comp. Neurol. 436, 182–201.
Giulian D., Corpuz M., Chapman S., Mansouri M., and Robertson C. (1993) Reactive mononuclear phagocytes release neurotoxins after ischemic and traumatic injury to the central nervous system. J. Neurosci. Res. 36, 681–693.
Fawcett J.W. and Geller H.M. (1998) Regeneration in the CNS: optimism mounts. Trends Neurosci. 21, 179–180.
Mallat M. and Chamak B. (1994) Brain macrophages: neurotoxic or neurotrophic effector cells? J. Leukoc. Biol. 56, 416–422.
Kreutzberg G.W. (1996) Microglia: a sensor for pathological events in the CNS. Trends Neurosci. 19, 312–318.
Baulac M., Rieger F., and Meninger V. (1983) The loss of motorneurons corresponding to specific muscles in the wobbler mutant mouse. Neurosci. Lett. 37, 99–104.
Ma W. and Vacca-Galloway L.L. (1991) Reduced branching and length of dendrites detected in cervical spinal cord motoneurons of wobbler mouse, a model for inherited motoneuron disease. J. Comp. Neurol. 311, 210–222
Newbery H.J. and Abbott C.M. (2001) Of mice, men and motor neurons. Trends Genet. 17, S2-S6.
Frugier T., Nicole S., Cifuente-Diaz C., and Melki J. (2002) The molecular bases of spinal muscular atrophy. Curr. Opin. Gen. Dev. 12, 294–298.
Jessell T.M. (2000) Neuronal specification in the spinal cord: inductive signals and transcriptional codes. Nat. Rev. Genet. 1, 20–29.
Lee S.K. and Pfaff S.L. (2001) Transcriptional networks regulating neuronal identity in the developing spinal cord. Nat. Neurosci. 4, 1183–1191.
La Vail J.H. and Irons K.P. (1988) Abnormal neuromuscular junctions in the lateral rectus of wobbler mice. Brain Res. 463, 78–89.
Toursel T., Bastide B., Stevens L., Rieger F., and Mounier Y. (2000) Alterations in contractile properties and expression of myofibrillar proteins in wobbler mouse muscle. Exp. Neurol. 162, 311–320.
Sedehizade F., Klocke R., and Jockusch H. (1997) Expression of nerve-regulated genes in muscles of mouse mutants affected by spinal muscular atrophies and muscular dystrophies. Muscle Nerve 20, 186–194.
Smith M.E. and Hughes S. (1994) POMC neuropeptides and their receptors in the neuromuscular system of wobbler mice. J. Neurochem. Sci. 124 Suppl, 56–58.
Hughes S. and Smith M.E. (1989) Proopiomelanocortin-derived peptides in mice with motoneurone disease. Neurosci. Lett. 103, 169–173.
Mandler R.N. and Baca J.M. (1992) Muscle lactate dehydrogenase activity is decreased in murin motor neuron disease. Brain Res. 576, 337–338.
Harris J.B. and Ward M.R. (1974) A comparative study of “denervation” in muscles from mice with inherited progressive neuromuscular disorders. Exp. Neurol. 42, 169–180.
Abe K., Morita S., Kikuchi T., and Itoyama Y. (1997) Protective effect of a novel free radical scavenger, OPC-14117, on wobbler mouse motor neuron disease. J. Neurosci. Res. 48, 63–70.
Mitsumoto H., Ikeda K., Holmlund T., Geene T., Cedarbaum J.M., Wong V., et al. (1994) The effects of Ciliary Neurotrophic Factor on motor dysfunction in wobbler mouse motor neuron disease. Ann. Neurol. 36, 142–148.
Ikeda K., Wong V., Holmlund T.H., Geene T., Cedarbaum J.M., Lindsay R.M., et al. Mitsumoto H. (1995) Histometric effects of ciliary neurotrophic factor in wobbler mouse motor neuron disease. Ann. Neurol. 37, 47–54.
Ikeda K., Klinkosz B., Geene T., Cedarbaum J.M., Wong V., Lindsay R.M., et al. (1995) Effects of Brain-derived Neurotrophic Factor on motor dysfunction in wobbler mouse motor neuron disease. Ann. Neurol. 37, 505–511.
Mitsumoto H., Ikeda K., Klinkosz B., Cedarbaum J.M., Wong V., and Lindsay R. (1994) Arrest of motor neuron disease in wobbler mice cotreated with CNTF and BDNF. Science 265, 1107–1110.
Ikeda K., Iwasaki Y., Tagaya N., Shiojima T., and Kinoshita M. (1995) Neuroprotective effect of cholinergic differentiation factor/Leukemia inhibitory factor on wobbler murine motor neuron disease. Muscle Nerve 18, 1344–1347.
Ikeda K., Kinoshita M., Tagaya N., Shiojima T., Taga T., Yasukawa K., et al. (1996) Coadministration of Interleukin-6 (IL-6) and soluble IL-6 receptor delays progression of wobbler mouse motor neuron disease. Brain Res. 726, 91–97.
Hantaï D., Akaaboune M., Lagord C., Murawsky M., Houenou L.J., Festoff B.W., et al. (1995) Beneficial effects of insulin-like growth factor-I on wobbler mouse motoneuron disease. J. Neurol. Sci. 129 Suppl, 123–126.
Vergani L., Finco C., Giulio A.M.D., Muller E.E., and Gorio A. (1997) Effects of low doses of glycosaminoglycans and insulin-like growth factor-I on motor neuron disease in wobbler mouse. Neurosci. Lett. 228, 41–44.
Vergani L., Losa M., lesma E., Giulio A.M.D., Torsello A., Müller E.E., et al. (1999) Glycosaminoglycans boost insulin-like growth factor-I-promoted neuroprotection: blockade of motor neuron death in the wobbler mouse. Neuroscience 93, 565–572.
Ikeda K., Iwasaki Y., Tagaya N., Shiojima T., Kobayashi T., and Kinoshita M. (1995) Neuroprotective effect of basic fibroblast growth factor on wobbler mouse motor neuron disease. Neurol. Res. 17, 445–448.
Mitsumoto H., Klinkosz B., Pioro E.P., Tsuzaka K., Ishiyama T., O’Leary R.M., et al. (2001) Effects of cardiotrophin-1 (CT-1) in a mouse motor neuron disease. Muscle Nerve 24, 769–777.
Krieger C., Perry T.L., Hansen S., Mitsumoto H., and Honoré T. (1992) Excitatory amino acid receptor antagonist in murin motoneuron disease (the wobbler mouse). Can. J. Neurol Sci. 19, 462–465.
Ikeda K., Iwasaki Y., Kinoshita M., Marubuchi S., and Ono S. (2000) T-588, a novel neuroprotective agent, delays progression of neuromuscular dysfunction in wobbler mouse motoneuron disease. Brain Res. 858, 84–91.
Kozachuk W.E., Mitsumoto H., Salanga V.D., Beck G.J., and Wilber J.F. (1987) Thyrotropin-releasing hormone (TRH) in murine motor neuron disease (the wobbler mouse). J. Neurol. Sci. 78, 253–260.
Ikeda K., Iwasaki Y., and Kinoshita M. (1998) JTP-2942, a novel thyrotropin-releasing hormone analogue, protects against spinal motor neuron degeneration in the wobbler mouse. Neurosci. Lett. 250, 9–12.
Lange D.J., Good P.F., and Bradley W.G. (1983) A therapeutic trial of gangliosides and thymosin in the wobbler mouse model of motor neuron disease. J. Neurol. Sci. 61, 211–216.
Bensimon G., Lacombez L., Meninger V., and group T.A.R.s. (1994) A controlled trial of riluzole in amyotrophic lateral sclerosis. N. Engl. J. Med. 330, 585–591.
Borasio G.D., Robberecht W., Leigh P.N., Emile J., Guiloff R.J., Jerusalem F., et al. (1998) A Placebo-controlled trial of insulin-like growth factor-I in amyotrophic lateral sclerosis. European ALS/IGF-I study group. Neurology 51, 583–586.
Desnuelle C., Dib M., Carrel C., and Favier A. (2001) A double-blind, placebo-controlled randomized clinical trial of alpha-tocopherol (vitamin E) in the treatment of amyotrophic lateral sclerosis. ALS riluzole-tocopherol study group. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 2, 9–18.
Group A.C.t.s. (1996) A double-blind placebo-controlled clinical trial of subcutaneous recombinant human ciliary neurotrophic factor (rHCNTF) in amyotrophic lateral sclerosis. Neurology. 46, 1244–1249.
Group B.S. (1999) A controlled trial of recombinant methionyl human BDNF in ALS: The BDNF study group (phase III). Neurology 52, 1427–1433.
Lacombez L., Bensimon G., N.Leigh P., Guillet P., and Meninger V. (1996) Dose-ranging study of riluzole in amyotrophic lateral sclerosis. Lancet 347, 1425–1431.
Lai E.C., Felice K.J., Festoff B.W., Gawel M.J., Gelinas D.F., Kratz R., et al. (1997) Effect of recombinant human insulin-like growth factor-I on progression of ALS. A placebo-controlled study. The North America ALS/IGF-I study group. Neurology 49, 1621–1630.
Louwerse E.S., Waverling G.J., Bossuyt P.M., Meyjes F.E., and Jong J.M.D. (1995) Randomized, double-blind, controlled trial of acetylcysteine in amyotrophic lateral sclerosis. Arch. Neurol. 52, 559–564.
Miller R.G., 2nd D.H.M., Gelinas D.F., Dronsky V., Mendoza M., Barohn R.J., et al. (2001) Phase III randomized trial of gabapentin in patients with amyotrophic lateral sclerosis. Neurology 56, 843–848.
Miller R.G., Petajan J.H., Bryan W.W., Armon C., Barohn R.J., Goodpasture J.C., et al. (1996) A placebo-controlled trial of recombinant human ciliary neurotrophic factor (rhCNTF) in amyotrophic lateral sclerosis. Ann. Neurol. 39, 256–260.
Ochs G., Penn R.D., York M., Giess R., Beck M., Tonn J., et al. (2000) A phase I/II trial of recombinant methionyl human brain derived neurotrophic factor administrated by intrathecal infusion to patients with amyotrophic lateral sclerosis. Amyotroph. Lateral Scler. Other Motor Neuron Disord. 1, 201–206.
Reider C.R. and Paulson G.W. (1997) Lou Gehrig and amyotrophic lateral sclerosis. Is vitamin E to be revisited? Arch. Neurol. 54, 527–528.
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Boillée, S., Peschanski, M. & Junier, MP. The wobbler mouse. Mol Neurobiol 28, 65–106 (2003). https://doi.org/10.1385/MN:28:1:65
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DOI: https://doi.org/10.1385/MN:28:1:65