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
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2008

Open Access 01-12-2008 | Research article

Dystrophin deficiency in canine X-linked muscular dystrophy in Japan (CXMDJ) alters myosin heavy chain expression profiles in the diaphragm more markedly than in the tibialis cranialis muscle

Authors: Katsutoshi Yuasa, Akinori Nakamura, Takao Hijikata, Shinichi Takeda

Published in: BMC Musculoskeletal Disorders | Issue 1/2008

Login to get access

Abstract

Background

Skeletal muscles are composed of heterogeneous collections of muscle fiber types, the arrangement of which contributes to a variety of functional capabilities in many muscle types. Furthermore, skeletal muscles can adapt individual myofibers under various circumstances, such as disease and exercise, by changing fiber types. This study was performed to examine the influence of dystrophin deficiency on fiber type composition of skeletal muscles in canine X-linked muscular dystrophy in Japan (CXMDJ), a large animal model for Duchenne muscular dystrophy.

Methods

We used tibialis cranialis (TC) muscles and diaphragms of normal dogs and those with CXMDJ at various ages from 1 month to 3 years old. For classification of fiber types, muscle sections were immunostained with antibodies against fast, slow, or developmental myosin heavy chain (MHC), and the number and size of these fibers were analyzed. In addition, MHC isoforms were detected by gel electrophoresis.

Results

In comparison with TC muscles of CXMDJ, the number of fibers expressing slow MHC increased markedly and the number of fibers expressing fast MHC decreased with growth in the affected diaphragm. In populations of muscle fibers expressing fast and/or slow MHC(s) but not developmental MHC of CXMDJ muscles, slow MHC fibers were predominant in number and showed selective enlargement. Especially, in CXMDJ diaphragms, the proportions of slow MHC fibers were significantly larger in populations of myofibers with non-expression of developmental MHC. Analyses of MHC isoforms also indicated a marked increase of type I and decrease of type IIA isoforms in the affected diaphragm at ages over 6 months. In addition, expression of developmental (embryonic and/or neonatal) MHC decreased in the CXMDJ diaphragm in adults, in contrast to continuous high-level expression in affected TC muscle.

Conclusion

The CXMDJ diaphragm showed marked changes in fiber type composition unlike TC muscles, suggesting that the affected diaphragm may be effectively adapted toward dystrophic stress by switching to predominantly slow fibers. Furthermore, the MHC expression profile in the CXMDJ diaphragm was markedly different from that in mdx mice, indicating that the dystrophic dog is a more appropriate model than a murine one, to investigate the mechanisms of respiratory failure in DMD.
Appendix
Available only for authorised users
Literature
1.
Emery AEH: Duchenne Muscular Dystrophy. 1993, Oxford: Oxford University Press, 2
2.
Nonaka I: Animal models of muscular dystrophies. Lab Anim Sci. 1998, 48: 8-17.PubMed
3.
Valentine BA, Cooper BJ, Cummings JF, De Lahunta A: Canine X-linked muscular dystrophy: morphologic lesions. J Neurol Sci. 1990, 97: 1-23. 10.1016/0022-510X(90)90095-5.CrossRefPubMed
4.
Howell JM, Fletcher S, Kakulas BA, O'Hara M, Lochmuller H, Karpati G: Use of the dog model for Duchenne muscular dystrophy in gene therapy trials. Neuromuscul Disord. 1997, 7: 325-328. 10.1016/S0960-8966(97)00057-6.CrossRefPubMed
5.
Shimatsu Y, Yoshimura M, Yuasa K, Urasawa N, Tomohiro M, Nakura M, Tanigawa M, Nakamura A, Takeda S: Major clinical and histopathological characteristics of canine X-linked muscular dystrophy in Japan, CXMDJ. Acta Myol. 2005, 24: 145-154.PubMed
6.
Shimatsu Y, Katagiri K, Furuta T, Nakura M, Tanioka Y, Yuasa K, Tomohiro M, Kornegay JN, Nonaka I, Takeda S: Canine X-linked muscular dystrophy in Japan (CXMDJ). Exp Anim. 2003, 52: 93-97. 10.1538/expanim.52.93.CrossRefPubMed
7.
Yugeta N, Urasawa N, Fujii Y, Yoshimura M, Yuasa K, Wada MR, Nakura M, Shimatsu Y, Tomohiro M, Takahashi A, Machida N, Wakao Y, Nakamura A, Takeda S: Cardiac involvement in Beagle-based canine X-linked muscular dystrophy in Japan (CXMDJ): electrocardiographic, echocardiographic, and morphologic studies. BMC Cardiovasc Disord. 2006, 6: 47-10.1186/1471-2261-6-47.CrossRefPubMedPubMedCentral
8.
Fukushima K, Nakamura A, Ueda H, Yuasa K, Yoshida K, Takeda S, Ikeda S: Activation and localization of matrix metalloproteinase-2 and -9 in the skeletal muscle of the muscular dystrophy dog (CXMDJ). BMC Musculoskelet Disord. 2007, 8: 54-10.1186/1471-2474-8-54.CrossRefPubMedPubMedCentral
9.
Yuasa K, Yoshimura M, Urasawa N, Ohshima S, Howell JM, Nakamura A, Hijikata T, Miyagoe-Suzuki Y, Takeda S: Injection of a recombinant AAV serotype 2 into canine skeletal muscles evokes strong immune responses against transgene products. Gene Ther. 2007, 14: 1249-1260. 10.1038/sj.gt.3302984.CrossRefPubMed
10.
Scott W, Stevens J, Binder-Macleod SA: Human skeletal muscle fiber type classifications. Phys Ther. 2001, 81: 1810-1816.PubMed
11.
Toniolo L, Maccatrozzo L, Patruno M, Pavan E, Caliaro F, Rossi R, Rinaldi C, Canepari M, Reggiani C, Mascarello F: Fiber types in canine muscles: myosin isoform expression and functional characterization. Am J Physiol Cell Physiol. 2007, 292: C1915-1926. 10.1152/ajpcell.00601.2006.CrossRefPubMed
12.
Marini JF, Pons F, Leger J, Loffreda N, Anoal M, Chevallay M, Fardeau M, Leger JJ: Expression of myosin heavy chain isoforms in Duchenne muscular dystrophy patients and carriers. Neuromuscul Disord. 1991, 1: 397-409. 10.1016/0960-8966(91)90003-B.CrossRefPubMed
13.
Muller J, Vayssiere N, Royuela M, Leger ME, Muller A, Bacou F, Pons F, Hugon G, Mornet D: Comparative evolution of muscular dystrophy in diaphragm, gastrocnemius and masseter muscles from old male mdx mice. J Muscle Res Cell Motil. 2001, 22: 133-139. 10.1023/A:1010305801236.CrossRefPubMed
14.
Lanfossi M, Cozzi F, Bugini D, Colombo S, Scarpa P, Morandi L, Galbiati S, Cornelio F, Pozza O, Mora M: Development of muscle pathology in canine X-linked muscular dystrophy. I. Delayed postnatal maturation of affected and normal muscle as revealed by myosin isoform analysis and utrophin expression. Acta Neuropathol. 1999, 97: 127-138. 10.1007/s004010050965.CrossRefPubMed
15.
Petrof BJ, Stedman HH, Shrager JB, Eby J, Sweeney HL, Kelly AM: Adaptations in myosin heavy chain expression and contractile function in dystrophic mouse diaphragm. Am J Physiol. 1993, 265: C834-841.PubMed
16.
Honeyman K, Carville KS, Howell JM, Fletcher S, Wilton SD: Development of a snapback method of single-strand conformation polymorphism analysis for genotyping Golden Retrievers for the X-linked muscular dystrophy allele. Am J Vet Res. 1999, 60: 734-737.PubMed
17.
Yuasa K, Sakamoto M, Miyagoe-Suzuki Y, Tanouchi A, Yamamoto H, Li J, Chamberlain JS, Xiao X, Takeda S: Adeno-associated virus vector-mediated gene transfer into dystrophin-deficient skeletal muscles evokes enhanced immune response against the transgene product. Gene Ther. 2002, 9: 1576-1588. 10.1038/sj.gt.3301829.CrossRefPubMed
18.
Butler-Browne GS, Whalen RG: Myosin isozyme transitions occurring during the postnatal development of the rat soleus muscle. Dev Biol. 1984, 102: 324-334. 10.1016/0012-1606(84)90197-0.CrossRefPubMed
19.
Hosaka Y, Yokota T, Miyagoe-Suzuki Y, Yuasa K, Imamura M, Matsuda R, Ikemoto T, Kameya S, Takeda S: Alpha1-syntrophin-deficient skeletal muscle exhibits hypertrophy and aberrant formation of neuromuscular junctions during regeneration. J Cell Biol. 2002, 158: 1097-1107. 10.1083/jcb.200204076.CrossRefPubMedPubMedCentral
20.
Agbulut O, Li Z, Mouly V, Butler-Browne GS: Analysis of skeletal and cardiac muscle from desmin knock-out and normal mice by high resolution separation of myosin heavy-chain isoforms. Biol Cell. 1996, 88: 131-135. 10.1016/S0248-4900(97)83528-9.CrossRefPubMed
21.
Webster C, Silberstein L, Hays AP, Blau HM: Fast muscle fibers are preferentially affected in Duchenne muscular dystrophy. Cell. 1988, 52: 503-513. 10.1016/0092-8674(88)90463-1.CrossRefPubMed
22.
Crow MT, Kushmerick MJ: Chemical energetics of slow- and fast-twitch muscles of the mouse. J Gen Physiol. 1982, 79: 147-166. 10.1085/jgp.79.1.147.CrossRefPubMed
23.
Gramolini AO, Belanger G, Thompson JM, Chakkalakal JV, Jasmin BJ: Increased expression of utrophin in a slow vs. a fast muscle involves posttranscriptional events. Am J Physiol Cell Physiol. 2001, 281: C1300-1309.PubMed
24.
Chakkalakal JV, Stocksley MA, Harrison MA, Angus LM, Deschenes-Furry J, St-Pierre S, Megeney LA, Chin ER, Michel RN, Jasmin BJ: Expression of utrophin A mRNA correlates with the oxidative capacity of skeletal muscle fiber types and is regulated by calcineurin/NFAT signaling. Proc Natl Acad Sci USA. 2003, 100: 7791-7796. 10.1073/pnas.0932671100.CrossRefPubMedPubMedCentral
25.
26.
Dunn SE, Burns JL, Michel RN: Calcineurin is required for skeletal muscle hypertrophy. J Biol Chem. 1999, 274: 21908-21912. 10.1074/jbc.274.31.21908.CrossRefPubMed
27.
Allen DL, Sartorius CA, Sycuro LK, Leinwand LA: Different pathways regulate expression of the skeletal myosin heavy chain genes. J Biol Chem. 2001, 276: 43524-43533. 10.1074/jbc.M108017200.CrossRefPubMed
28.
Stupka N, Michell BJ, Kemp BE, Lynch GS: Differential calcineurin signalling activity and regeneration efficacy in diaphragm and limb muscles of dystrophic mdx mice. Neuromuscul Disord. 2006, 16: 337-346. 10.1016/j.nmd.2006.03.003.CrossRefPubMed
29.
Spangenburg EE, Booth FW: Molecular regulation of individual skeletal muscle fiber types. Acta Physiol Scand. 2003, 178: 413-424. 10.1046/j.1365-201X.2003.01158.x.CrossRefPubMed
30.
Michel RN, Dunn SE, Chin ER: Calcineurin and skeletal muscle growth. Proc Nutr Soc. 2004, 63: 341-349. 10.1079/PNS2004362.CrossRefPubMed
31.
Valentine BA, Cooper BJ: Canine X-linked muscular dystrophy: selective involvement of muscles in neonatal dogs. Neuromuscul Disord. 1991, 1: 31-38. 10.1016/0960-8966(91)90040-Y.CrossRefPubMed
32.
Chin ER, Olson EN, Richardson JA, Yang Q, Humphries C, Shelton JM, Wu H, Zhu W, Bassel-Duby R, Williams RS: A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type. Genes Dev. 1998, 12: 2499-509.CrossRefPubMedPubMedCentral
33.
Lupu F, Terwilliger JD, Lee K, Segre GV, Efstratiadis A: Roles of growth hormone and insulin-like growth factor 1 in mouse postnatal growth. Dev Biol. 2001, 229: 141-162. 10.1006/dbio.2000.9975.CrossRefPubMed
34.
Coirault C, Lambert F, Marchand-Adam S, Attal P, Chemla D, Lecarpentier Y: Myosin molecular motor dysfunction in dystrophic mouse diaphragm. Am J Physiol. 1999, 277: C1170-1176.PubMed
35.
Polla B, D'Antona G, Bottinelli R, Reggiani C: Respiratory muscle fibres: specialisation and plasticity. Thorax. 2004, 59: 808-817. 10.1136/thx.2003.009894.CrossRefPubMedPubMedCentral
36.
Snow DH, Billeter R, Mascarello F, Carpene E, Rowlerson A, Jenny E: No classical type IIB fibres in dog skeletal muscle. Histochemistry. 1982, 75: 53-65. 10.1007/BF00492533.CrossRefPubMed
Metadata
Title
Dystrophin deficiency in canine X-linked muscular dystrophy in Japan (CXMDJ) alters myosin heavy chain expression profiles in the diaphragm more markedly than in the tibialis cranialis muscle
Authors
Katsutoshi Yuasa
Akinori Nakamura
Takao Hijikata
Shinichi Takeda
Publication date
01-12-2008
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2008
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/1471-2474-9-1

Other articles of this Issue 1/2008

BMC Musculoskeletal Disorders 1/2008 Go to the issue

Research article

Carpal tunnel syndrome and the use of computer mouse and keyboard: A systematic review

Research article

Natural course of intra-articular shifting bone marrow edema syndrome of the knee

Research article

Reliability and validity of the short questionnaire to assess health-enhancing physical activity (SQUASH) in patients after total hip arthroplasty

Study protocol

Bracing Patients with Idiopathic Scoliosis: Design of the Dutch Randomized Controlled Treatment Trial

Research article

Effect of tadalafil on blood flow, pain, and function in chronic cold Complex Regional Pain Syndrome: a randomized controlled trial

Study protocol

Exercise and manual auricular acupuncture: a pilot assessor-blind randomised controlled trial. (The acupuncture and personalised exercise programme (APEP) Trial)