Evaluation of the dystrophin carboxy-terminal domain for micro-dystrophin gene therapy in cardiac and skeletal muscles in the DMD

Animals Chromatography, Liquid Dystrophin / genetics Dystrophin-Associated Protein Complex / metabolism Genetic Therapy Muscle, Skeletal / metabolism Muscular Dystrophy, Duchenne / genetics Rats Tandem Mass Spectrometry

Journal

Gene therapy

ISSN: 1476-5462

Titre abrégé: Gene Ther

Pays: England

ID NLM: 9421525

Informations de publication

Date de publication:
Sep 2022

Historique:

received: 12 04 2021

accepted: 13 01 2022

revised: 09 12 2021

pubmed: 3 2 2022

medline: 21 9 2022

entrez: 2 2 2022

Statut: ppublish

Résumé

Duchenne muscular dystrophy (DMD) is a muscle wasting disorder caused by mutations in the gene encoding dystrophin. Gene therapy using micro-dystrophin (MD) transgenes and recombinant adeno-associated virus (rAAV) vectors hold great promise. To overcome the limited packaging capacity of rAAV vectors, most MD do not include dystrophin carboxy-terminal (CT) domain. Yet, the CT domain is known to recruit α1- and β1-syntrophins and α-dystrobrevin, a part of the dystrophin-associated protein complex (DAPC), which is a signaling and structural mediator of muscle cells. In this study, we explored the impact of inclusion of the dystrophin CT domain on ΔR4-23/ΔCT MD (MD1), in DMD

Identifiants

DOI: 10.1038/s41434-022-00317-6 PMID: 35105949

pubmed: 35105949

doi: 10.1038/s41434-022-00317-6

pii: 10.1038/s41434-022-00317-6

doi:

Substances chimiques

Dystrophin 0

Dystrophin-Associated Protein Complex 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

520-535

Commentaires et corrections

Type : CommentIn

Informations de copyright

Références

Mendell JR, Lloyd-Puryear M. Report of MDA muscle disease symposium on newborn screening for Duchenne muscular dystrophy. Muscle Nerve. 2013;48:21–6.

pubmed: 23716304 doi: 10.1002/mus.23810

Hoffman EP, Brown RH, Kunkel LM. Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell. 1987;51:919–28.

pubmed: 3319190 doi: 10.1016/0092-8674(87)90579-4

Bhat HF, Mir SS, Dar KB, Bhat ZF, Shah RA, Ganai NA. ABC of multifaceted dystrophin glycoprotein complex (DGC). J Cell Physiol. 2018;233:5142–59.

pubmed: 28464259 doi: 10.1002/jcp.25982

Ervasti JM, Ohlendieck K, Kahl SD, Gaver MG, Campbell KP. Deficiency of a glycoprotein component of the dystrophin complex in dystrophic muscle. Nature. 1990;345:315–9.

pubmed: 2188135 doi: 10.1038/345315a0

Bushby K, Finkel R, Birnkrant DJ, Case LE, Clemens PR, Cripe L, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol. 2010;9:77–93.

pubmed: 19945913 doi: 10.1016/S1474-4422(09)70271-6

Wang D, Zhong L, Nahid MA, Gao G. The potential of adeno-associated viral vectors for gene delivery to muscle tissue. Expert Opin Drug Deliv. 2014;11:345–64.

pubmed: 24386892 pmcid: 4098646 doi: 10.1517/17425247.2014.871258

Rivera VM, Gao G, Grant RL, Schnell MA, Zoltick PW, Rozamus LW, et al. Long-term pharmacologically regulated expression of erythropoietin in primates following AAV-mediated gene transfer. Blood. 2005;105:1424–30.

pubmed: 15507527 doi: 10.1182/blood-2004-06-2501

Wu Z, Yang H, Colosi P. Effect of genome size on AAV vector packaging. Mol Ther Janv. 2010;18:80–6.

doi: 10.1038/mt.2009.255

Harper SQ, Hauser MA, DelloRusso C, Duan D, Crawford RW, Phelps SF, et al. Modular flexibility of dystrophin: Implications for gene therapy of Duchenne muscular dystrophy. Nat Med. 2002;8:253–61.

pubmed: 11875496 doi: 10.1038/nm0302-253

Athanasopoulos T, Graham I, Foster H, Dickson G. Recombinant adeno-associated viral (rAAV) vectors as therapeutic tools for Duchenne muscular dystrophy (DMD). Gene Ther. 2004;11:S109–21.

pubmed: 15454965 doi: 10.1038/sj.gt.3302379

Muntoni F, Torelli S, Ferlini A. Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol. 2003;2:731–40.

pubmed: 14636778 doi: 10.1016/S1474-4422(03)00585-4

Gregorevic P, Allen JM, Minami E, Blankinship MJ, Haraguchi M, Meuse L, et al. rAAV6-microdystrophin preserves muscle function and extends lifespan in severely dystrophic mice. Nat Med. 2006;12:787–9.

pubmed: 16819550 pmcid: 4244883 doi: 10.1038/nm1439

Foster H, Sharp PS, Athanasopoulos T, Trollet C, Graham IR, Foster K, et al. Codon and mRNA sequence optimization of microdystrophin transgenes improves expression and physiological outcome in dystrophic mdx mice following AAV2/8 Gene Transfer. Mol Ther. 2008;16:1825–32.

pubmed: 18766174 doi: 10.1038/mt.2008.186

Bostick B, Yue Y, Lai Y, Long C, Li D, Duan D. Adeno-associated virus serotype-9 microdystrophin gene therapy ameliorates electrocardiographic abnormalities in mdx mice. Hum Gene Ther. 2008;19:851–6.

pubmed: 18666839 pmcid: 2888653 doi: 10.1089/hum.2008.058

Yue Y, Pan X, Hakim CH, Kodippili K, Zhang K, Shin J-H, et al. Safe and bodywide muscle transduction in young adult Duchenne muscular dystrophy dogs with adeno-associated virus. Hum Mol Genet. 2015;24:5880–90.

pubmed: 26264580 pmcid: 4581611 doi: 10.1093/hmg/ddv310

Le Guiner C, Servais L, Montus M, Larcher T, Fraysse B, Moullec S, et al. Long-term microdystrophin gene therapy is effective in a canine model of Duchenne muscular dystrophy. Nat Commun. 2017;8:16105.

pubmed: 28742067 pmcid: 5537486 doi: 10.1038/ncomms16105

Hakim CH, Wasala NB, Pan X, Kodippili K, Yue Y, Zhang K, et al. A five-repeat micro-dystrophin gene ameliorated dystrophic phenotype in the severe DBA/2J-mdx model of duchenne muscular dystrophy. Mol Ther Methods Clin Dev. 2017;6:216–30.

pubmed: 28932757 pmcid: 5596503 doi: 10.1016/j.omtm.2017.06.006

Duan D, Systemic AAV. Micro-dystrophin gene therapy for duchenne muscular dystrophy. Mol Ther. 2018;26:2337–56.

pubmed: 30093306 pmcid: 6171037 doi: 10.1016/j.ymthe.2018.07.011

Lai Y, Thomas GD, Yue Y, Yang HT, Li D, Long C, et al. Dystrophins carrying spectrin-like repeats 16 and 17 anchor nNOS to the sarcolemma and enhance exercise performance in a mouse model of muscular dystrophy. J Clin Invest. 2009;119:624–35.

pubmed: 19229108 pmcid: 2648692 doi: 10.1172/JCI36612

Gregorevic P, Blankinship MJ, Allen JM, Chamberlain JS. Systemic microdystrophin gene delivery improves skeletal muscle structure and function in old dystrophic mdx mice. Mol Ther. 2008;16:657–64.

pubmed: 18334986 doi: 10.1038/mt.2008.28

Shin J-H, Nitahara-Kasahara Y, Hayashita-Kinoh H, Ohshima-Hosoyama S, Kinoshita K, Chiyo T. et al. Improvement of cardiac fibrosis in dystrophic mice by rAAV9-mediated microdystrophin transduction. Gene Ther. 2011;18:910–9.

pubmed: 21451578 doi: 10.1038/gt.2011.36

Bostick B, Shin J-H, Yue Y, Duan D. AAV-microdystrophin therapy improves cardiac performance in aged female mdx mice. Mol Ther. 2011;19:1826–32.

pubmed: 21811246 pmcid: 3188746 doi: 10.1038/mt.2011.154

Wang B, Li J, Fu FH, Xiao X. Systemic human minidystrophin gene transfer improves functions and life span of dystrophin and dystrophin/utrophin-deficient mice. J Orthopaedic Res. 2009;27:421–6.

doi: 10.1002/jor.20781

Guiner CL, McIntyre M, Larcher T, Adjali O, Lafoux A, Toumaniantz G, et al. Dose finding study in the DMDmdx rat model to determine the efficacious dose of a rAAV9 vector encoding a human mini-dystrophin after IV administration. Neuromuscular Disorders. 2017;27:S188.

doi: 10.1016/j.nmd.2017.06.344

Mendell JR, Sahenk Z, Lehman K, Nease C, Lowes LP, Miller NF, et al. Assessment of Systemic Delivery of rAAVrh74.MHCK7.micro-dystrophin in Children With Duchenne Muscular Dystrophy: A Nonrandomized Controlled Trial. JAMA Neurol. 2020;77:1122–31.

pubmed: 32539076 doi: 10.1001/jamaneurol.2020.1484

Moorehead T, Yong F, Neelakantan S, Beaverson K, Binks M. Safety and tolerability of PF-06939926 in ambulatory boys with duchenne muscular dystrophy: a phase 1b multicenter, open- label, dose ascending study. Mol Ther J Am Soc Gene Ther. 2020;28:272.

Koo T. Studies on gene transfer in skeletal muscle cells and tissues using recombinant adeno-associated virus (AAV) vectors. Thesis. 2010.

Suzuki A, Yoshida M, Ozawa E. Mammalian alpha 1- and beta 1-syntrophin bind to the alternative splice-prone region of the dystrophin COOH terminus. J Cell Biol. 1995;128:373–81.

pubmed: 7844151 doi: 10.1083/jcb.128.3.373

Sadoulet-Puccio HM, Rajala M, Kunkel LM. Dystrobrevin and dystrophin: an interaction through coiled-coil motifs. Proc Natl Acad Sci USA. 1997;94:12413–8.

pubmed: 9356463 pmcid: 24974 doi: 10.1073/pnas.94.23.12413

Yoshida M, Hama H, Ishikawa-Sakurai M, Imamura M, Mizuno Y, Araishi K, et al. Biochemical evidence for association of dystrobrevin with the sarcoglycan-sarcospan complex as a basis for understanding sarcoglycanopathy. Hum Mol Genet. 2000;9:1033–40.

pubmed: 10767327 doi: 10.1093/hmg/9.7.1033

Bhat HF, Adams ME, Khanday FA. Syntrophin proteins as Santa Claus: role(s) in cell signal transduction. Cell Mol Life Sci. 2013;70:2533–54.

pubmed: 23263165 doi: 10.1007/s00018-012-1233-9

Matamoros M, Pérez-Hernández M, Guerrero-Serna G, Amorós I, Barana A, Núñez M, et al. Nav1.5 N-terminal domain binding to α1-syntrophin increases membrane density of human Kir2.1, Kir2.2 and Nav1.5 channels. Cardiovasc Res. 2016;110:279–90.

pubmed: 26786162 pmcid: 4836625 doi: 10.1093/cvr/cvw009

Leyva-Leyva M, Sandoval A, Felix R, González-Ramírez R. Biochemical and functional interplay between ion channels and the components of the dystrophin-associated glycoprotein complex. J Membr Biol. 2018;251:535–50.

pubmed: 29779049 doi: 10.1007/s00232-018-0036-9

Sabourin J, Lamiche C, Vandebrouck A, Magaud C, Rivet J, Cognard C, et al. Regulation of TRPC1 and TRPC4 cation channels requires an α1-syntrophin-dependent complex in skeletal mouse myotubes. J Biol Chem. 2009;284:36248–61.

pubmed: 19812031 pmcid: 2794741 doi: 10.1074/jbc.M109.012872

Vandebrouck A, Sabourin J, Rivet J, Balghi H, Sebille S, Kitzis A, et al. Regulation of capacitative calcium entries by alpha1-syntrophin: association of TRPC1 with dystrophin complex and the PDZ domain of alpha1-syntrophin. FASEB J. 2007;21:608–17.

pubmed: 17202249 doi: 10.1096/fj.06-6683com

Dombernowsky NW, Ölmestig JNE, Witting N, Kruuse C. Role of neuronal nitric oxide synthase (nNOS) in Duchenne and Becker muscular dystrophies - Still a possible treatment modality? Neuromuscul Disord. 2018;28:914–26.

pubmed: 30352768 doi: 10.1016/j.nmd.2018.09.001

Crawford GE, Faulkner JA, Crosbie RH, Campbell KP, Froehner SC, Chamberlain JS. Assembly of the dystrophin-associated protein complex does not require the dystrophin cooh-terminal domain. J Cell Biol. 2000;150:1399–410.

pubmed: 10995444 pmcid: 2150715 doi: 10.1083/jcb.150.6.1399

Koo T, Malerba A, Athanasopoulos T, Trollet C, Boldrin L, Ferry A, et al. Delivery of AAV2/9-microdystrophin genes incorporating helix 1 of the coiled-coil motif in the C-Terminal domain of dystrophin improves muscle pathology and restores the level of α1-syntrophin and α-dystrobrevin in skeletal muscles of mdx mice. Hum Gene Ther. 2011;22:1379–88.

pubmed: 21453126 pmcid: 3225045 doi: 10.1089/hum.2011.020

McGreevy JW, Hakim CH, McIntosh MA, Duan D. Animal models of Duchenne muscular dystrophy: from basic mechanisms to gene therapy. Dis Model Mech. 2015;8:195–213.

pubmed: 25740330 pmcid: 4348559 doi: 10.1242/dmm.018424

Tandon A, Jefferies JL, Villa CR, Hor KN, Wong BL, Ware SM, et al. Dystrophin genotype-cardiac phenotype correlations in Duchenne and Becker muscular dystrophies using cardiac magnetic resonance imaging. Am J Cardiol. 2015;115:967–71.

pubmed: 25702278 pmcid: 5568575 doi: 10.1016/j.amjcard.2015.01.030

Johnson EK, Zhang L, Adams ME, Phillips A, Freitas MA, Froehner SC, et al. Proteomic analysis reveals new cardiac-specific dystrophin-associated proteins. PLoS ONE. 2012;7:e43515.

pubmed: 22937058 pmcid: 3427372 doi: 10.1371/journal.pone.0043515

Larcher T, Lafoux A, Tesson L, Remy S, Thepenier V, François V, et al. Characterization of dystrophin deficient rats: a new model for Duchenne muscular dystrophy. PLoS ONE. 2014;9:e110371.

pubmed: 25310701 pmcid: 4195719 doi: 10.1371/journal.pone.0110371

Li X, Eastman EM, Schwartz RJ, Draghia-Akli R. Synthetic muscle promoters: activities exceeding naturally occurring regulatory sequences. Nat Biotechnol. 1999;17:241–5.

pubmed: 10096290 doi: 10.1038/6981

D’Costa S, Blouin V, Broucque F, Penaud-Budloo M, François A, Perez IC, et al. Practical utilization of recombinant AAV vector reference standards: focus on vector genomes titration by free ITR qPCR. Mol Ther Methods Clin Dev. 2016;5:16019.

pubmed: 27069952 pmcid: 4813604 doi: 10.1038/mtm.2016.19

Salvetti A, Orève S, Chadeuf G, Favre D, Cherel Y, Champion-Arnaud P, et al. Factors influencing recombinant adeno-associated virus production. Hum Gene Ther. 1998;9:695–706.

pubmed: 9551617 doi: 10.1089/hum.1998.9.5-695

Shinoda K, Tomita M, Ishihama Y. emPAI Calc—for the estimation of protein abundance from large-scale identification data by liquid chromatography-tandem mass spectrometry. Bioinformatics. 2010;26:576–7.

pubmed: 20031975 doi: 10.1093/bioinformatics/btp700

Ishihama Y, Oda Y, Tabata T, Sato T, Nagasu T, Rappsilber J, et al. Exponentially modified protein abundance index (emPAI) for estimation of absolute protein amount in proteomics by the number of sequenced peptides per protein. Mol Cell Proteomics. 2005;4:1265–72.

pubmed: 15958392 doi: 10.1074/mcp.M500061-MCP200

Fraysse B, Desaphy J-F, Rolland J-F, Pierno S, Liantonio A, Giannuzzi V, et al. Fiber type-related changes in rat skeletal muscle calcium homeostasis during aging and restoration by growth hormone. Neurobiol Dis. 2006;21:372–80.

pubmed: 16153853 doi: 10.1016/j.nbd.2005.07.012

Louch WE, Sheehan KA, Wolska BM. Methods in cardiomyocyte isolation, culture, and gene transfer. J Mol Cell Cardiol. 2011;51:288–98.

pubmed: 21723873 pmcid: 3164875 doi: 10.1016/j.yjmcc.2011.06.012

Grynkiewicz G, Poenie M, Tsien RY. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985;260:3440–50.

pubmed: 3838314 doi: 10.1016/S0021-9258(19)83641-4

Dyle MC, Ebert SM, Cook DP, Kunkel SD, Fox DK, Bongers KS, et al. Systems-based discovery of tomatidine as a natural small molecule inhibitor of skeletal muscle atrophy. J Biol Chem. 2014;289:14913–24.

pubmed: 24719321 pmcid: 4031541 doi: 10.1074/jbc.M114.556241

Moorwood C, Liu M, Tian Z, Barton ER. Isometric and eccentric force generation assessment of skeletal muscles isolated from murine models of muscular dystrophies. J Vis Exp. 2013;31:e50036.

Chapdelaine P, Gérard C, Sanchez N, Cherif K, Rousseau J, Ouellet DL, et al. Development of an AAV9 coding for a 3XFLAG-TALEfrat#8-VP64 able to increase in vivo the human frataxin in YG8R mice. Gene Ther. 2016;23:606–14.

pubmed: 27082765 pmcid: 4940929 doi: 10.1038/gt.2016.36

Mayra A, Tomimitsu H, Kubodera T, Kobayashi M, Piao W, Sunaga F, et al. Intraperitoneal AAV9-shRNA inhibits target expression in neonatal skeletal and cardiac muscles. Biochem Biophys Res Commun. 2011;405:204–9.

pubmed: 21219850 doi: 10.1016/j.bbrc.2011.01.009

Madhavan R, Jarrett HW. Phosphorylation of dystrophin and alpha-syntrophin by Ca(2+)-calmodulin dependent protein kinase II. Biochim Biophys Acta. 1999;1434:260–74.

pubmed: 10525145 doi: 10.1016/S0167-4838(99)00193-4

Madhavan R, Jarrett HW. Calmodulin-activated phosphorylation of dystrophin. Biochemistry. 1994;33:5797–804.

pubmed: 8180208 doi: 10.1021/bi00185a018

Sato S, Omori Y, Katoh K, Kondo M, Kanagawa M, Miyata K, et al. Pikachurin, a dystroglycan ligand, is essential for photoreceptor ribbon synapse formation. Nat Neurosci. 2008;11:923–31.

pubmed: 18641643 doi: 10.1038/nn.2160

Pacak CA, Mah CS, Thattaliyath BD, Conlon TJ, Lewis MA, Cloutier DE, et al. Recombinant adeno-associated virus serotype 9 leads to preferential cardiac transduction in vivo. Circ Res. 2006;99:e3–9.

pubmed: 16873720 doi: 10.1161/01.RES.0000237661.18885.f6

Banks GB, Judge LM, Allen JM, Chamberlain JS. The polyproline site in hinge 2 influences the functional capacity of truncated dystrophins. PLoS Genet. 2010;6:e1000958.

pubmed: 20502633 pmcid: 2873924 doi: 10.1371/journal.pgen.1000958

Lorin C, Vögeli I, Niggli E. Dystrophic cardiomyopathy: role of TRPV2 channels in stretch-induced cell damage. Cardiovasc Res. 2015;106:153–62.

pubmed: 25616416 doi: 10.1093/cvr/cvv021

Parekh AB, Penner R. Store depletion and calcium influx. Physiol Rev. 1997;77:901–30.

pubmed: 9354808 doi: 10.1152/physrev.1997.77.4.901

Hermans MCE, Pinto YM, Merkies ISJ, de Die-Smulders CEM, Crijns HJGM, Faber CG. Hereditary muscular dystrophies and the heart. Neuromuscul Disord. 2010;20:479–92.

pubmed: 20627570 doi: 10.1016/j.nmd.2010.04.008

Szabó PL, Ebner J, Koenig X, Hamza O, Watzinger S, Trojanek S, et al. Cardiovascular phenotype of the Dmdmdx rat - a suitable animal model for Duchenne muscular dystrophy. Dis Model Mech. 2021;22:14.

England SB, Nicholson LV, Johnson MA, Forrest SM, Love DR, Zubrzycka-Gaarn EE, et al. Very mild muscular dystrophy associated with the deletion of 46% of dystrophin. Nature. 1990;343:180–2.

pubmed: 2404210 doi: 10.1038/343180a0

Yue Y, Liu M, Duan D. C-Terminal-Truncated microdystrophin recruits dystrobrevin and syntrophin to the dystrophin-associated glycoprotein complex and reduces muscular dystrophy in symptomatic utrophin/dystrophin double-knockout mice. Mol Ther. 2006;14:79–87.

pubmed: 16563874 doi: 10.1016/j.ymthe.2006.01.007

Nakamori M, Takahashi MP. The role of α-dystrobrevin in striated muscle. Int J Mol Sci. 2011;12:1660–71.

pubmed: 21673914 pmcid: 3111625 doi: 10.3390/ijms12031660

Ishikawa-Sakurai M, Yoshida M, Imamura M, Davies KE, Ozawa EZZ. domain is essentially required for the physiological binding of dystrophin and utrophin to beta-dystroglycan. Hum Mol Genet. 2004;13:693–702.

pubmed: 14962982 doi: 10.1093/hmg/ddh087

Johnson EK, Li B, Yoon JH, Flanigan KM, Martin PT, Ervasti J, et al. Identification of new dystroglycan complexes in skeletal muscle. PLoS ONE. 2013;8:e73224.

pubmed: 23951345 pmcid: 3738564 doi: 10.1371/journal.pone.0073224

Liu L. Lessons from cavin-1 deficiency. Biochem Soc Trans. 2020;48:147–54.

pubmed: 31922193 pmcid: 7080641 doi: 10.1042/BST20190380

Taniguchi T, Maruyama N, Ogata T, Kasahara T, Nakanishi N, Miyagawa K, et al. PTRF/Cavin-1 deficiency causes cardiac dysfunction accompanied by cardiomyocyte hypertrophy and cardiac fibrosis. PLoS ONE. 2016;11:e0162513.

pubmed: 27612189 pmcid: 5017623 doi: 10.1371/journal.pone.0162513

Kaakinen M, Reichelt ME, Ma Z, Ferguson C, Martel N, Porrello ER, et al. Cavin-1 deficiency modifies myocardial and coronary function, stretch responses and ischaemic tolerance: roles of NOS over-activity. Basic Res Cardiol. 2017;112:24.

pubmed: 28343262 doi: 10.1007/s00395-017-0613-6

Bostick B, Yue Y, Long C, Marschalk N, Fine DM, Chen J, et al. Cardiac expression of a mini-dystrophin that normalizes skeletal muscle force only partially restores heart function in aged mdx mice. Mol Ther. 2009;17:253–61.

pubmed: 19066599 doi: 10.1038/mt.2008.264

Banks GB, Combs AC, Chamberlain JR, Chamberlain JS. Molecular and cellular adaptations to chronic myotendinous strain injury in mdx mice expressing a truncated dystrophin. Hum Mol Genet. 2008;17:3975–86.

pubmed: 18799475 pmcid: 2638580 doi: 10.1093/hmg/ddn301

Banks GB, Chamberlain JS, Froehner SC. Truncated dystrophins can influence neuromuscular synapse structure. Mol Cell Neurosci. 2009;40:433–41.

pubmed: 19171194 pmcid: 2826111 doi: 10.1016/j.mcn.2008.12.011

Sawicka E. Origin of the ring muscle fibers in neuromuscular diseases. Neuropatologia Polska. 1991;29:29–40.

pubmed: 1839930

Sekiguchi M. The role of dystrophin in the central nervous system: a mini review. Acta Myol: Myopathies and Cardiomyopathies: Official Journal of the Mediterranean Society of Myology. 2005;24:93–7.

Haenggi T, Fritschy J-M. Role of dystrophin and utrophin for assembly and function of the dystrophin glycoprotein complex in non-muscle tissue. Cell Mol Life Sci: CMLS. 2006;63:1614–31.

pubmed: 16710609 doi: 10.1007/s00018-005-5461-0

Chen L, Zhang J, Hu X, Philipson KD, Scharf SM. The Na+/Ca2+ exchanger-1 mediates left ventricular dysfunction in mice with chronic intermittent hypoxia. J Appl Physiol (1985). 2010;109:1675–85.

doi: 10.1152/japplphysiol.01372.2009