Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

ACC 2024 Congress

Catch up on all the top stories and latest evidence in cardiology research with our ACC 2024 Congress hub page.
ADVANCED SEARCH
Log in
Top
Molecular Neurodegeneration
Published in: Molecular Neurodegeneration 1/2018

Open Access 01-12-2018 | Research article

Transcriptional profiling and biomarker identification reveal tissue specific effects of expanded ataxin-3 in a spinocerebellar ataxia type 3 mouse model

Authors: Lodewijk J. A. Toonen, Maurice Overzier, Melvin M. Evers, Leticia G. Leon, Sander A. J. van der Zeeuw, Hailiang Mei, Szymon M. Kielbasa, Jelle J. Goeman, Kristina M. Hettne, Olafur Th. Magnusson, Marion Poirel, Alexandre Seyer, Peter A. C. ‘t Hoen, Willeke M. C. van Roon-Mom

Published in: Molecular Neurodegeneration | Issue 1/2018

Login to get access

Abstract

Background

Spinocerebellar ataxia type 3 (SCA3) is a progressive neurodegenerative disorder caused by expansion of the polyglutamine repeat in the ataxin-3 protein. Expression of mutant ataxin-3 is known to result in transcriptional dysregulation, which can contribute to the cellular toxicity and neurodegeneration. Since the exact causative mechanisms underlying this process have not been fully elucidated, gene expression analyses in brains of transgenic SCA3 mouse models may provide useful insights.

Methods

Here we characterised the MJD84.2 SCA3 mouse model expressing the mutant human ataxin-3 gene using a multi-omics approach on brain and blood. Gene expression changes in brainstem, cerebellum, striatum and cortex were used to study pathological changes in brain, while blood gene expression and metabolites/lipids levels were examined as potential biomarkers for disease.

Results

Despite normal motor performance at 17.5 months of age, transcriptional changes in brain tissue of the SCA3 mice were observed. Most transcriptional changes occurred in brainstem and striatum, whilst cerebellum and cortex were only modestly affected. The most significantly altered genes in SCA3 mouse brain were Tmc3, Zfp488, Car2, and Chdh. Based on the transcriptional changes, α-adrenergic and CREB pathways were most consistently altered for combined analysis of the four brain regions. When examining individual brain regions, axon guidance and synaptic transmission pathways were most strongly altered in striatum, whilst brainstem presented with strongest alterations in the pi-3 k cascade and cholesterol biosynthesis pathways. Similar to other neurodegenerative diseases, reduced levels of tryptophan and increased levels of ceramides, di- and triglycerides were observed in SCA3 mouse blood.

Conclusions

The observed transcriptional changes in SCA3 mouse brain reveal parallels with previous reported neuropathology in patients, but also shows brain region specific effects as well as involvement of adrenergic signalling and CREB pathway changes in SCA3. Importantly, the transcriptional changes occur prior to onset of motor- and coordination deficits.
Appendix
Available only for authorised users
Literature
1.
Riess O, Rub U, Pastore A, Bauer P, Schols L. SCA3: neurological features, pathogenesis and animal models. Cerebellum. 2008;7:125–37.CrossRefPubMed
2.
Evers MM, Toonen LJ, van Roon-Mom WM. Ataxin-3 protein and RNA toxicity in spinocerebellar ataxia type 3: current insights and emerging therapeutic strategies. Mol Neurobiol. 2014;49:1513–31.PubMed
3.
Matos CA, de Macedo-Ribeiro S, Carvalho AL. Polyglutamine diseases: the special case of ataxin-3 and Machado-Joseph disease. Prog Neurobiol. 2011;95:26–48.CrossRefPubMed
4.
Bichelmeier U, Schmidt T, Hubener J, Boy J, Ruttiger L, Habig K, Poths S, Bonin M, Knipper M, Schmidt WJ, et al. Nuclear localization of ataxin-3 is required for the manifestation of symptoms in SCA3: in vivo evidence. J Neurosci. 2007;27:7418–28.CrossRefPubMed
5.
Paulson HL, Perez MK, Trottier Y, Trojanowski JQ, Subramony SH, Das SS, Vig P, Mandel JL, Fischbeck KH, Pittman RN. Intranuclear inclusions of expanded polyglutamine protein in spinocerebellar ataxia type 3. Neuron. 1997;19:333–44.CrossRefPubMed
6.
Chai Y, Koppenhafer SL, Shoesmith SJ, Perez MK, Paulson HL. Evidence for proteasome involvement in polyglutamine disease: localization to nuclear inclusions in SCA3/MJD and suppression of polyglutamine aggregation in vitro. Hum Mol Genet. 1999;8:673–82.CrossRefPubMed
7.
Yu YC, Kuo CL, Cheng WL, Liu CS, Hsieh M. Decreased antioxidant enzyme activity and increased mitochondrial DNA damage in cellular models of Machado-Joseph disease. J Neurosci Res. 2009;87:1884–91.CrossRefPubMed
8.
Chou AH, Yeh TH, Ouyang P, Chen YL, Chen SY, Wang HL. Polyglutamine-expanded ataxin-3 causes cerebellar dysfunction of SCA3 transgenic mice by inducing transcriptional dysregulation. Neurobiol Dis. 2008;31:89–101.CrossRefPubMed
9.
Perez MK, Paulson HL, Pendse SJ, Saionz SJ, Bonini NM, Pittman RN. Recruitment and the role of nuclear localization in polyglutamine-mediated aggregation. J Cell Biol. 1998;143:1457–70.CrossRefPubMedPubMedCentral
10.
Nucifora FC Jr, Sasaki M, Peters MF, Huang H, Cooper JK, Yamada M, Takahashi H, Tsuji S, Troncoso J, Dawson VL, et al. Interference by huntingtin and atrophin-1 with cbp-mediated transcription leading to cellular toxicity. Science (New York, NY). 2001;291:2423–8.CrossRef
11.
Evert BO, Vogt IR, Kindermann C, Ozimek L, de Vos RA, Brunt ER, Schmitt I, Klockgether T, Wullner U. Inflammatory genes are upregulated in expanded ataxin-3-expressing cell lines and spinocerebellar ataxia type 3 brains. J Neurosci. 2001;21:5389–96.CrossRefPubMed
12.
Evert BO, Vogt IR, Vieira-Saecker AM, Ozimek L, de Vos RA, Brunt ER, Klockgether T, Wullner U. Gene expression profiling in ataxin-3 expressing cell lines reveals distinct effects of normal and mutant ataxin-3. J Neuropathol Exp Neurol. 2003;62:1006–18.CrossRefPubMed
13.
Trancikova A, Ramonet D, Moore DJ. Genetic mouse models of neurodegenerative diseases. Prog Mol Biol Transl Sci. 2011;100:419–82.CrossRefPubMed
14.
Mastrokolias A, Pool R, Mina E, Hettne KM, van Duijn E, van der Mast RC, van Ommen G, t Hoen PA, Prehn C, Adamski J, van Roon-Mom W. Integration of targeted metabolomics and transcriptomics identifies deregulation of phosphatidylcholine metabolism in Huntington’s disease peripheral blood samples. Metabolomics. 2016;12:137.CrossRefPubMedPubMedCentral
15.
Mina E, van Roon-Mom W, Hettne K, van Zwet E, Goeman J, Neri C, ACtH P, Mons B, Roos M. Common disease signatures from gene expression analysis in Huntington’s disease human blood and brain. Orphanet journal of rare diseases. 2016;11:97.CrossRefPubMedPubMedCentral
16.
Cemal CK, Carroll CJ, Lawrence L, Lowrie MB, Ruddle P, Al-Mahdawi S, King RH, Pook MA, Huxley C, Chamberlain S. YAC transgenic mice carrying pathological alleles of the MJD1 locus exhibit a mild and slowly progressive cerebellar deficit. Hum Mol Genet. 2002;11:1075–94.CrossRefPubMed
17.
Gardiner SL, van Belzen MJ, Boogaard MW, van Roon-Mom WMC, Rozing MP, van Hemert AM, Smit JH, Beekman ATF, van Grootheest G, Schoevers RA, et al. Huntingtin gene repeat size variations affect risk of lifetime depression. Transl Psychiatry. 2017;7:1277.CrossRefPubMedPubMedCentral
18.
Boudah S, Olivier MF, Aros-Calt S, Oliveira L, Fenaille F, Tabet JC, Junot C. Annotation of the human serum metabolome by coupling three liquid chromatography methods to high-resolution mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2014;966:34–47.CrossRefPubMed
19.
Dunn WB, Broadhurst D, Begley P, Zelena E, Francis-McIntyre S, Anderson N, Brown M, Knowles JD, Halsall A, Haselden JN, et al. Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry. Nat Protoc. 2011;6:1060–83.CrossRefPubMed
20.
Seyer A, Boudah S, Broudin S, Junot C, Colsch B. Annotation of the human cerebrospinal fluid lipidome using high resolution mass spectrometry and a dedicated data processing workflow. Metabolomics. 2016;12:91.CrossRefPubMedPubMedCentral
21.
Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR. STAR: ultrafast universal RNA-seq aligner. Bioinformatics (Oxford, England). 2013;29:15–21.CrossRef
22.
Robinson MD, McCarthy DJ, Smyth GK. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics (Oxford, England). 2010;26:139–40.CrossRef
23.
24.
Hansen KD, Irizarry RA, Wu Z. Removing technical variability in RNA-seq data using conditional quantile normalization. Biostatistics (Oxford, England). 2012;13:204–16.CrossRef
25.
Wickham H. ggplot2: Elegant Graphics for Data Analysis. In: Book ggplot2: Elegant Graphics for Data Analysis. New York: Springer-Verlag; 2009.CrossRef
26.
27.
28.
Toonen LJ, Schmidt I, Luijsterburg MS, van Attikum H, van Roon-Mom WM. Antisense oligonucleotide-mediated exon skipping as a strategy to reduce proteolytic cleavage of ataxin-3. Sci Rep. 2016;6:35200.CrossRefPubMedPubMedCentral
29.
Rozen S, Skaletsky H. Primer3 on the WWW for general users and for biologist programmers. Methods Mol Biol. 2000;132:365–86.PubMed
30.
Ruijter JM, Ramakers C, Hoogaars WM, Karlen Y, Bakker O, van den Hoff MJ, Moorman AF. Amplification efficiency: linking baseline and bias in the analysis of quantitative PCR data. Nucleic Acids Res. 2009;37:e45.CrossRefPubMedPubMedCentral
31.
Shaywitz AJ, Greenberg ME. CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu Rev Biochem. 1999;68:821–61.CrossRefPubMed
32.
Wyttenbach A, Swartz J, Kita H, Thykjaer T, Carmichael J, Bradley J, Brown R, Maxwell M, Schapira A, Orntoft TF, et al. Polyglutamine expansions cause decreased CRE-mediated transcription and early gene expression changes prior to cell death in an inducible cell model of Huntington’s disease. Hum Mol Genet. 2001;10:1829–45.CrossRefPubMed
33.
Giralt A, Saavedra A, Carreton O, Xifro X, Alberch J, Perez-Navarro E. Increased PKA signaling disrupts recognition memory and spatial memory: role in Huntington’s disease. Hum Mol Genet. 2011;20:4232–47.CrossRefPubMed
34.
Saura CA, Valero J. The role of CREB signaling in Alzheimer’s disease and other cognitive disorders. Rev Neurosci. 2011;22:153–69.CrossRefPubMed
35.
Alberini CM. Transcription factors in long-term memory and synaptic plasticity. Physiol Rev. 2009;89:121–45.CrossRefPubMed
36.
Leoni V, Caccia C. The impairment of cholesterol metabolism in Huntington disease. Biochim Biophys Acta. 2015;1851:1095–105.CrossRefPubMed
37.
Block RC, Dorsey ER, Beck CA, Brenna JT, Shoulson I. Altered cholesterol and fatty acid metabolism in Huntington disease. J Clin Lipidol. 2010;4:17–23.CrossRefPubMedPubMedCentral
38.
Bartzokis G, Lu PH, Tishler TA, Fong SM, Oluwadara B, Finn JP, Huang D, Bordelon Y, Mintz J, Perlman S. Myelin breakdown and iron changes in Huntington’s disease: pathogenesis and treatment implications. Neurochem Res. 2007;32:1655–64.CrossRefPubMed
39.
Nishiyama K, Murayama S, Goto J, Watanabe M, Hashida H, Katayama S, Nomura Y, Nakamura S, Kanazawa I. Regional and cellular expression of the Machado-Joseph disease gene in brains of normal and affected individuals. Ann Neurol. 1996;40:776–81.CrossRefPubMed
40.
Ingram M, Wozniak EA, Duvick L, Yang R, Bergmann P, Carson R, O’Callaghan B, Zoghbi HY, Henzler C, Orr HT. Cerebellar transcriptome profiles of ATXN1 transgenic mice reveal SCA1 disease progression and protection pathways. Neuron. 2016;89:1194–207.CrossRefPubMedPubMedCentral
41.
Serra HG, Byam CE, Lande JD, Tousey SK, Zoghbi HY, Orr HT. Gene profiling links SCA1 pathophysiology to glutamate signaling in Purkinje cells of transgenic mice. Hum Mol Genet. 2004;13:2535–43.CrossRefPubMed
42.
Chou AH, Chen CY, Chen SY, Chen WJ, Chen YL, Weng YS, Wang HL. Polyglutamine-expanded ataxin-7 causes cerebellar dysfunction by inducing transcriptional dysregulation. Neurochem Int. 2010;56:329–39.CrossRefPubMed
43.
44.
Raposo M, Bettencourt C, Maciel P, Gao F, Ramos A, Kazachkova N, Vasconcelos J, Kay T, Rodrigues AJ, Bettencourt B, et al. Novel candidate blood-based transcriptional biomarkers of Machado-Joseph disease. Move Disord. 2015;30:968–75.CrossRef
45.
Denis U, Lecomte M, Paget C, Ruggiero D, Wiernsperger N, Lagarde M. Advanced glycation end-products induce apoptosis of bovine retinal pericytes in culture: involvement of diacylglycerol/ceramide production and oxidative stress induction. Free Radic Biol Med. 2002;33:236–47.CrossRefPubMed
46.
Ruvolo PP. Ceramide regulates cellular homeostasis via diverse stress signaling pathways. Leukemia. 2001;15:1153–60.CrossRefPubMed
47.
Kori M, Aydin B, Unal S, Arga KY, Kazan D. Metabolic biomarkers and neurodegeneration: a pathway enrichment analysis of Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. Omics. 2016;20:645–61.CrossRefPubMed
48.
Mastrokolias A, Ariyurek Y, Goeman JJ, van Duijn E, Roos RA, van der Mast RC, van Ommen GB, den Dunnen JT, t Hoen PA, van Roon-Mom WM. Huntington’s disease biomarker progression profile identified by transcriptome sequencing in peripheral blood. Eur J Human Genetics. 2015;23:1349–56.CrossRef
49.
Chen CM, Wu YR, Cheng ML, Liu JL, Lee YM, Lee PW, Soong BW, Chiu DT. Increased oxidative damage and mitochondrial abnormalities in the peripheral blood of Huntington’s disease patients. Biochem Biophys Res Commun. 2007;359:335–40.CrossRefPubMed
50.
Kazachkova N, Raposo M, Montiel R, Cymbron T, Bettencourt C, Silva-Fernandes A, Silva S, Maciel P, Lima M. Patterns of mitochondrial DNA damage in blood and brain tissues of a transgenic mouse model of Machado-Joseph disease. Neurodegener Dis. 2013;11:206–14.CrossRefPubMed
51.
Sen NE, Drost J, Gispert S, Torres-Odio S, Damrath E, Klinkenberg M, Hamzeiy H, Akdal G, Gulluoglu H, Basak AN, Auburger G. Search for SCA2 blood RNA biomarkers highlights Ataxin-2 as strong modifier of the mitochondrial factor PINK1 levels. Neurobiol Dis. 2016;96:115–26.CrossRefPubMed
52.
Forrest CM, Mackay GM, Stoy N, Spiden SL, Taylor R, Stone TW, Darlington LG. Blood levels of kynurenines, interleukin-23 and soluble human leucocyte antigen-G at different stages of Huntington’s disease. J Neurochem. 2010;112:112–22.CrossRefPubMed
53.
Widner B, Leblhuber F, Walli J, Tilz GP, Demel U, Fuchs D. Degradation of tryptophan in neurodegenerative disorders. Adv Exp Med Biol. 1999;467:133–8.CrossRefPubMed
54.
Schwarcz R, Okuno E, White RJ, Bird ED, Whetsell WO Jr. 3-Hydroxyanthranilate oxygenase activity is increased in the brains of Huntington disease victims. Proc Natl Acad Sci U S A. 1988;85:4079–81.CrossRefPubMedPubMedCentral
55.
Pacheco LS, da Silveira AF, Trott A, Houenou LJ, Algarve TD, Bello C, Lenz AF, Manica-Cattani MF, da Cruz IB. Association between Machado-Joseph disease and oxidative stress biomarkers. Mutat Res. 2013;757:99–103.CrossRefPubMed
56.
Zhang N, Li B, Al-Ramahi I, Cong X, Held JM, Kim E, Botas J, Gibson BW, Ellerby LM. Inhibition of lipid signaling enzyme diacylglycerol kinase epsilon attenuates mutant huntingtin toxicity. J Biol Chem. 2012;287:21204–13.CrossRefPubMedPubMedCentral
57.
58.
Arboleda G, Morales LC, Benitez B, Arboleda H. Regulation of ceramide-induced neuronal death: cell metabolism meets neurodegeneration. Brain Res Rev. 2009;59:333–46.CrossRefPubMed
59.
Posse de Chaves EI. Sphingolipids in apoptosis, survival and regeneration in the nervous system. Biochim Biophys Acta. 2006;1758:1995–2015.CrossRefPubMed
60.
Cutler RG, Pedersen WA, Camandola S, Rothstein JD, Mattson MP. Evidence that accumulation of ceramides and cholesterol esters mediates oxidative stress-induced death of motor neurons in amyotrophic lateral sclerosis. Ann Neurol. 2002;52:448–57.CrossRefPubMed
61.
Lee CF, Chern Y. Adenosine receptors and Huntington’s disease. Int Rev Neurobiol. 2014;119:195–232.CrossRefPubMed
62.
Chou AH, Chen YL, Chiu CC, Yuan SJ, Weng YH, Yeh TH, Lin YL, Fang JM, Wang HL. T1-11 and JMF1907 ameliorate polyglutamine-expanded ataxin-3-induced neurodegeneration, transcriptional dysregulation and ataxic symptom in the SCA3 transgenic mouse. Neuropharmacology. 2015;99:308–17.CrossRefPubMed
63.
Li F, Macfarlan T, Pittman RN, Chakravarti D. Ataxin-3 is a histone-binding protein with two independent transcriptional corepressor activities. J Biol Chem. 2002;277:45004–12.CrossRefPubMed
64.
McCampbell A, Taylor JP, Taye AA, Robitschek J, Li M, Walcott J, Merry D, Chai Y, Paulson H, Sobue G, Fischbeck KH. CREB-binding protein sequestration by expanded polyglutamine. Hum Mol Genet. 2000;9:2197–202.CrossRefPubMed
65.
Shimohata M, Shimohata T, Igarashi S, Naruse S, Tsuji S. Interference of CREB-dependent transcriptional activation by expanded polyglutamine stretches--augmentation of transcriptional activation as a potential therapeutic strategy for polyglutamine diseases. J Neurochem. 2005;93:654–63.CrossRefPubMed
66.
Iijima-Ando K, Wu P, Drier EA, Iijima K, Yin JC. cAMP-response element-binding protein and heat-shock protein 70 additively suppress polyglutamine-mediated toxicity in Drosophila. Proc Natl Acad Sci U S A. 2005;102:10261–6.CrossRefPubMedPubMedCentral
67.
Kwok RP, Lundblad JR, Chrivia JC, Richards JP, Bachinger HP, Brennan RG, Roberts SG, Green MR, Goodman RH. Nuclear protein CBP is a coactivator for the transcription factor CREB. Nature. 1994;370:223–6.CrossRefPubMed
68.
Oliner JD, Andresen JM, Hansen SK, Zhou S, Tjian R. SREBP transcriptional activity is mediated through an interaction with the CREB-binding protein. Genes Dev. 1996;10:2903–11.CrossRefPubMed
69.
Steffan JS, Kazantsev A, Spasic-Boskovic O, Greenwald M, Zhu YZ, Gohler H, Wanker EE, Bates GP, Housman DE, Thompson LM. The Huntington’s disease protein interacts with p53 and CREB-binding protein and represses transcription. Proc Natl Acad Sci U S A. 2000;97:6763–8.CrossRefPubMedPubMedCentral
70.
Shakkottai VG, do Carmo Costa M, Dell’Orco JM, Sankaranarayanan A, Wulff H, Paulson HL. Early changes in cerebellar physiology accompany motor dysfunction in the polyglutamine disease spinocerebellar ataxia type 3. J Neurosci. 2011;31:13002–14.CrossRefPubMedPubMedCentral
71.
Costa Mdo C, Luna-Cancalon K, Fischer S, Ashraf NS, Ouyang M, Dharia RM, Martin-Fishman L, Yang Y, Shakkottai VG, Davidson BL, et al. Toward RNAi therapy for the polyglutamine disease Machado-Joseph disease. Mol Therapy. 2013;21:1898–908.CrossRef
72.
Chen X, Tang TS, Tu H, Nelson O, Pook M, Hammer R, Nukina N, Bezprozvanny I. Deranged calcium signaling and neurodegeneration in spinocerebellar ataxia type 3. J Neurosci. 2008;28:12713–24.CrossRefPubMedPubMedCentral
73.
Toonen LJA, Rigo F, van Attikum H, van Roon-Mom WMC. Antisense oligonucleotide-mediated removal of the Polyglutamine repeat in spinocerebellar Ataxia type 3 mice. Mol Ther Nucleic Acids. 2017;8:232–42.CrossRefPubMedPubMedCentral
74.
Moore LJ, Nilsen TO, Jarungsriapisit J, Fjelldal PG, Stefansson SO, Taranger GL, Patel S. Triploid atlantic salmon (Salmo salar L.) post-smolts accumulate prevalence more slowly than diploid salmon following bath challenge with salmonid alphavirus subtype 3. PLoS One. 2017;12:e0175468.CrossRefPubMedPubMedCentral
75.
Schmidt T, Landwehrmeyer GB, Schmitt I, Trottier Y, Auburger G, Laccone F, Klockgether T, Volpel M, Epplen JT, Schols L, Riess O. An isoform of ataxin-3 accumulates in the nucleus of neuronal cells in affected brain regions of SCA3 patients. Brain Pathol (Zurich, Switzerland). 1998;8:669–79.CrossRef
76.
Wullner U, Reimold M, Abele M, Burk K, Minnerop M, Dohmen BM, Machulla HJ, Bares R, Klockgether T. Dopamine transporter positron emission tomography in spinocerebellar ataxias type 1, 2, 3, and 6. Arch Neurol. 2005;62:1280–5.CrossRefPubMed
77.
Nicola SM, Surmeier J, Malenka RC. Dopaminergic modulation of neuronal excitability in the striatum and nucleus accumbens. Annu Rev Neurosci. 2000;23:185–215.CrossRefPubMed
78.
Watabe-Uchida M, Zhu L, Ogawa SK, Vamanrao A, Uchida N. Whole-brain mapping of direct inputs to midbrain dopamine neurons. Neuron. 2012;74:858–73.CrossRefPubMed
79.
Andersson M, Konradi C, Cenci MA. cAMP response element-binding protein is required for dopamine-dependent gene expression in the intact but not the dopamine-denervated striatum. J Neurosci. 2001;21:9930–43.CrossRefPubMedPubMedCentral
80.
Pflieger LT, Dansithong W, Paul S, Scoles DR, Figueroa KP, Meera P, Otis TS, Facelli JC, Pulst SM. Gene co-expression network analysis for identifying modules and functionally enriched pathways in SCA2. Hum Mol Genet. 2017;26:3069–80.CrossRefPubMedPubMedCentral
81.
Ramani B, Panwar B, Moore LR, Wang B, Huang R, Guan Y, Paulson HL. Comparison of spinocerebellar ataxia type 3 mouse models identifies early gain-of-function, cell-autonomous transcriptional changes in oligodendrocytes. Hum Mol Genet. 2017;26:3362–74.CrossRefPubMedPubMedCentral
82.
Kida E, Palminiello S, Golabek AA, Walus M, Wierzba-Bobrowicz T, Rabe A, Albertini G, Wisniewski KE. Carbonic anhydrase II in the developing and adult human brain. J Neuropathol Exp Neurol. 2006;65:664–74.CrossRefPubMed
83.
Cammer W, Zhang H, Tansey FA. Effects of carbonic anhydrase II (CAII) deficiency on CNS structure and function in the myelin-deficient CAII-deficient double mutant mouse. J Neurosci Res. 1995;40:451–7.CrossRefPubMed
84.
Ghandour MS, Skoff RP, Venta PJ, Tashian RE. Oligodendrocytes express a normal phenotype in carbonic anhydrase II-deficient mice. J Neurosci Res. 1989;23:180–90.CrossRefPubMed
85.
Soundarapandian MM, Selvaraj V, Lo UG, Golub MS, Feldman DH, Pleasure DE, Deng W. Zfp488 promotes oligodendrocyte differentiation of neural progenitor cells in adult mice after demyelination. Sci Rep. 2011;1:2.CrossRefPubMedPubMedCentral
Metadata
Title
Transcriptional profiling and biomarker identification reveal tissue specific effects of expanded ataxin-3 in a spinocerebellar ataxia type 3 mouse model
Authors
Lodewijk J. A. Toonen
Maurice Overzier
Melvin M. Evers
Leticia G. Leon
Sander A. J. van der Zeeuw
Hailiang Mei
Szymon M. Kielbasa
Jelle J. Goeman
Kristina M. Hettne
Olafur Th. Magnusson
Marion Poirel
Alexandre Seyer
Peter A. C. ‘t Hoen
Willeke M. C. van Roon-Mom
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Molecular Neurodegeneration / Issue 1/2018
Electronic ISSN: 1750-1326
DOI
https://doi.org/10.1186/s13024-018-0261-9

Other articles of this Issue 1/2018

Molecular Neurodegeneration 1/2018 Go to the issue

Review

A new hypothesis for Parkinson’s disease pathogenesis: GTPase-p38 MAPK signaling and autophagy as convergence points of etiology and genomics

Commentary

Vibrational spectroscopy: a promising approach to discriminate neurodegenerative disorders

Research article

PU.1 regulates Alzheimer’s disease-associated genes in primary human microglia

Review

New insights into the role of TREM2 in Alzheimer’s disease

Research article

Tissue-enhanced plasma proteomic analysis for disease stratification in amyotrophic lateral sclerosis

Research article

Pathological phosphorylation of tau and TDP-43 by TTBK1 and TTBK2 drives neurodegeneration