Rescue of cardiomyopathy through U7snRNA-mediated exon skipping in Mybpc3-targeted knock-in mice

EMBO Molecular Medicine

Volumn 5, Issue 7, 2013, Pages 1060-1077

  Gedicke Hornung, Christina ^a,b   Behrens Gawlik, Verena ^a,b   Reischmann, Silke ^a,b   Geertz, Birgit ^a,b   Stimpel, Doreen ^a,b   Weinberger, Florian ^a,b   Schlossarek, Saskia ^a,b   Précigout, Guillaume ^c,d   Braren, Ingke ^a,b   Eschenhagen, Thomas ^a,b   Mearini, Giulia ^a,b   Lorain, Stéphanie ^c,d   Voit, Thomas ^c,d   Dreyfus, Patrick A ^c,d   Garcia, Luis ^c,d   Carrier, Lucie ^a,b,c,d  

^a UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^b DZHK GERMAN CENTRE FOR CARDIOVASCULAR RESEARCH   (Germany)

^c Sorbonne Université   (France)

^d SORBONNE UNIVERSITÉ   (France)

Author keywords

Alternative splicing; Antisense oligoribonucleotide; Cardiac myosin binding protein C; Exon skipping; Hypertrophic cardiomyopathy

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; MESSENGER RNA; SMALL NUCLEAR RNA;

ADENO ASSOCIATED VIRUS; ALTERNATIVE RNA SPLICING; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DRUG EFFICACY; EXON; EXON SKIPPING; GENE DELETION; GENE EXPRESSION; GENE SILENCING; GENE TARGETING; GENETIC VARIABILITY; HEART LEFT VENTRICLE HYPERTROPHY; HEART MUSCLE CELL; HYPERTROPHIC CARDIOMYOPATHY; IMMUNOFLUORESCENCE; IN VITRO STUDY; IN VIVO GENE TRANSFER; IN VIVO STUDY; MOUSE; NEWBORN; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROGNOSIS; PROTEIN PHOSPHORYLATION; THERAPY EFFECT; TRANSTHORACIC ECHOCARDIOGRAPHY; VIRAL GENE DELIVERY SYSTEM; VIRAL GENE THERAPY; WESTERN BLOTTING; WILD TYPE;

ALTERNATIVE SPLICING; ANTISENSE OLIGORIBONUCLEOTIDE; CARDIAC MYOSIN-BINDING PROTEIN-C; EXON SKIPPING; HYPERTROPHIC CARDIOMYOPATHY;

ADENOVIRIDAE; ALTERNATIVE SPLICING; ANIMALS; CARDIOMYOPATHY, HYPERTROPHIC; CARRIER PROTEINS; EXONS; GENE KNOCK-IN TECHNIQUES; GENETIC THERAPY; HEART; HEK293 CELLS; HUMANS; HYPERTROPHY, LEFT VENTRICULAR; MICE; MUTATION; MYOCARDIUM; OLIGORIBONUCLEOTIDES, ANTISENSE; PROTEIN ISOFORMS; RNA, MESSENGER; RNA, SMALL NUCLEAR; TRANSDUCTION, GENETIC;

EID: 84879998021     PISSN: 17574676     EISSN: 17574684     Source Type: Journal    
DOI: 10.1002/emmm.201202168     Document Type: Article

References (61)

1. Aartsma-Rus A, Janson AA, Kaman WE, Bremmer-Bout M, van Ommen GJ, den Dunnen JT, van Deutekom JC (2004) Antisense-induced multiexon skipping for Duchenne muscular dystrophy makes more sense. Am J Hum Genet 74: 83-92
2. Aartsma-Rus A, Janson AA, van Ommen GJ, van Deutekom JC (2007) Antisense-induced exon skipping for duplications in Duchenne muscular dystrophy. BMC Med Genet 8: 43
3. Aartsma-Rus A, van Ommen GJ (2007) Antisense-mediated exon skipping: a versatile tool with therapeutic and research applications. Rna 13: 1609-1624
4. Barbash IM, Cecchini S, Faranesh AZ, Virag T, Li L, Yang Y, Hoyt RF, Kornegay JN, Bogan JR, Garcia L, et al (2012) MRI roadmap-guided transendocardial delivery of exon-skipping recombinant adeno-associated virus restores dystrophin expression in a canine model of Duchenne muscular dystrophy. Gene Ther 20: 274-282
5. Barefield D, Sadayappan S (2010) Phosphorylation and function of cardiac myosin binding protein-C in health and disease. J Mol Cell Cardiol 48: 866-875
6. Bish LT, Sleeper MM, Forbes SC, Wang B, Reynolds C, Singletary GE, Trafny D, Morine KJ, Sanmiguel J, Cecchini S, et al (2012) Long-term restoration of cardiac dystrophin expression in golden retriever muscular dystrophy following rAAV6-mediated exon skipping. Mol Ther 20: 580-589
7. Bremmer-Bout M, Aartsma-Rus A, de Meijer EJ, Kaman WE, Janson AA, Vossen RH, van Ommen GJ, den Dunnen JT, van Deutekom JC (2004) Targeted exon skipping in transgenic hDMD mice: a model for direct preclinical screening of human-specific antisense oligonucleotides. Mol Ther 10: 232-240
8. Cartegni L, Wang J, Zhu Z, Zhang MQ, Krainer AR (2003) ESEfinder: a web resource to identify exonic splicing enhancers. Nucleic Acids Res 31: 3568-3571
9. Colson BA, Bekyarova T, Fitzsimons DP, Irving TC, Moss RL (2007) Radial displacement of myosin cross-bridges in mouse myocardium due to ablation of myosin binding protein-C. J Mol Biol 367: 36-41
10. Denti MA, Incitti T, Sthandier O, Nicoletti C, De Angelis FG, Rizzuto E, Auricchio A, Musaro A, Bozzoni I (2008) Long-term benefit of adeno-associated virus/antisense-mediated exon skipping in dystrophic mice. Hum Gene Ther 19: 601-608
11. Dominguez E, Marais T, Chatauret N, Benkhelifa-Ziyyat S, Duque S, Ravassard P, Carcenac R, Astord S, Pereira de Moura A, Voit T, et al (2011) Intravenous scAAV9 delivery of a codon-optimized SMN1 sequence rescues SMA mice. Hum Mol Genet 20: 681-693
12. Ehlermann P, Weichenhan D, Zehelein J, Steen H, Pribe R, Zeller R, Lehrke S, Zugck C, Ivandic BT, Katus HA (2008) Adverse events in families with hypertrophic or dilated cardiomyopathy and mutations in the MYBPC3 gene. BMC Med Genet 9: 95
13. El-Armouche A, Pohlmann L, Schlossarek S, Starbatty J, Yeh YH, Nattel S, Dobrev D, Eschenhagen T, Carrier L (2007) Decreased phosphorylation levels of cardiac myosin-binding protein-C in human and experimental heart failure. J Mol Cell Cardiol 43: 223-229
14. Elliott P, Andersson B, Arbustini E, Bilinska Z, Cecchi F, Charron P, Dubourg O, Kuhl U, Maisch B, McKenna WJ, et al (2008) Classification of the cardiomyopathies: a position statement from the European Society of Cardiology Working Group on myocardial and pericardial diseases. Eur Heart J 29: 270-276
15. Fatkin D, Christe ME, Aristizabal O, McConnell BK, Srinivasan S, Schoen FJ, Seidman CE, Turnbull DH, Seidman JG (1999) Neonatal cardiomyopathy in mice homozygous for the Arg403Gln mutation in the alpha cardiac myosin heavy chain gene. J Clin Invest 103: 147-153
16. Fougerousse F, Delezoide AL, Fiszman MY, Schwartz K, Beckmann JS, Carrier L (1998) Cardiac myosin binding protein C gene is specifically expressed in heart during murine and human development. Circ Res 82: 130-133
17. Fraysse B, Weinberger F, Bardswell SC, Cuello F, Vignier N, Geertz B, Starbatty J, Kramer E, Coirault C, Eschenhagen T, et al (2012) Increased myofilament Ca(2+) sensitivity and diastolic dysfunction as early consequences of Mybpc3 mutation in heterozygous knock-in mice. J Mol Cell Cardiol 52: 1299-1307
18. Galli G, Hofstetter H, Stunnenberg HG, Birnstiel ML (1983) Biochemical complementation with RNA in the Xenopus oocyte: a small RNA is required for the generation of 3' histone mRNA termini. Cell 34: 823-828
19. Gautel M, Fürst DO, Cocco A, Schiaffino S (1998) Isoform transitions of the myosin-binding protein C family in developing human and mouse muscles. Lack of isoform transcomplementation in cardiac muscle. Circ Res 82: 124-129
20. Gersh BJ, Maron BJ, Bonow RO, Dearani JA, Fifer MA, Link MS, Naidu SS, Nishimura RA, Ommen SR, Rakowski H et al (2011) ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Thorac Cardiovasc Surg 142: e153-203
21. Goemans NM, Tulinius M, van den Akker JT, Burm BE, Ekhart PF, Heuvelmans N, Holling T, Janson AA, Platenburg GJ, Sipkens JA, et al (2011) Systemic administration of PRO051 in Duchenne's muscular dystrophy. N Engl J Med 364: 1513-1522
22. Goyenvalle A, Babbs A, Wright J, Wilkins V, Powell D, Garcia L, Davies KE (2012a) Rescue of severely affected dystrophin/utrophin-deficient mice through scAAV-U7snRNA-mediated exon skipping. Hum Mol Genet 21: 2559-2571
23. Goyenvalle A, Vulin A, Fougerousse F, Leturcq F, Kaplan JC, Garcia L, Danos O (2004) Rescue of dystrophic muscle through U7 snRNA-mediated exon skipping. Science 306: 1796-1799
24. Goyenvalle A, Wright J, Babbs A, Wilkins V, Garcia L, Davies KE (2012b) Engineering multiple U7snRNA constructs to induce single and multiexon-skipping for Duchenne muscular dystrophy. Mol Ther 20: 1212-1221
25. Grimm D, Kay MA, Kleinschmidt JA (2003) Helper virus-free, optically controllable, and two-plasmid-based production of adeno-associated virus vectors of serotypes 1 to 6. Mol Ther 7: 839-850
26. Heemskerk HA, de Winter CL, de Kimpe SJ, van Kuik-Romeijn P, Heuvelmans N, Platenburg GJ, van Ommen GJ, van Deutekom JC, Aartsma-Rus A (2009) In vivo comparison of 2'-O-methyl phosphorothioate and morpholino antisense oligonucleotides for Duchenne muscular dystrophy exon skipping. J Gene Med 11: 257-266
27. Hu C, Lipshutz GS (2012) AAV-based neonatal gene therapy for hemophilia A: long-term correction and avoidance of immune responses in mice. Gene Ther 19: 1166-1176
28. Inagaki K, Fuess S, Storm TA, Gibson GA, McTiernan CF, Kay MA, Nakai H (2006) Robust systemic transduction with AAV9 vectors in mice: efficient global cardiac gene transfer superior to that of AAV8. Mol Ther 14: 45-53
29. Le Roy F, Charton K, Lorson CL, Richard I (2009) RNA-targeting approaches for neuromuscular diseases. Trends Mol Med 15: 580-591
30. Lu QL, Mann CJ, Lou F, Bou-Gharios G, Morris GE, Xue SA, Fletcher S, Partridge TA, Wilton SD (2003) Functional amounts of dystrophin produced by skipping the mutated exon in the mdx dystrophic mouse. Nat Med 9: 1009-1014
31. Lu QL, Rabinowitz A, Chen YC, Yokota T, Yin H, Alter J, Jadoon A, Bou-Gharios G, Partridge T (2005) Systemic delivery of antisense oligoribonucleotide restores dystrophin expression in body-wide skeletal muscles. Proc Natl Acad Sci USA 102: 198-203
32. Lu QL, Yokota T, Takeda S, Garcia L, Muntoni F, Partridge T (2011) The status of exon skipping as a therapeutic approach to Duchenne muscular dystrophy. Mol Ther 19: 9-15
33. Madden HR, Fletcher S, Davis MR, Wilton SD (2009) Characterization of a complex Duchenne muscular dystrophy-causing dystrophin gene inversion and restoration of the reading frame by induced exon skipping. Hum Mutat 30: 22-28
34. Maron BJ, Gardin JM, Flack JM, Gidding SS, Kurosaki TT, Bild DE (1995) Prevalence of hypertrophic cardiomyopathy in a general population of young adults. Echocardiographic analysis of 4111 subjects in the CARDIA Study. Coronary artery risk development in (young) adults. Circulation 92: 785-789
35. Maron BJ, Poliac LC, Roberts WO (1996) Risk for sudden cardiac death associated with marathon running. J Am Coll Cardiol 28: 428-431
36. Marston S, Copeland O, Jacques A, Livesey K, Tsang V, McKenna WJ, Jalilzadeh S, Carballo S, Redwood C, Watkins H (2009) Evidence from human myectomy samples that MYBPC3 mutations cause hypertrophic cardiomyopathy through haploinsufficiency. Circ Res 105: 219-222
37. Marston S, Copeland O, Gehmlich K, Schlossarek S, Carrier L (2012) How do MYBPC3 mutations cause hypertrophic cardiomyopathy? J Muscle Res Cell Motil (in press)
38. McClorey G, Moulton HM, Iversen PL, Fletcher S, Wilton SD (2006) Antisense oligonucleotide-induced exon skipping restores dystrophin expression in vitro in a canine model of DMD. Gene Ther 13: 1373-1381
39. McConnell BK, Jones KA, Fatkin D, Arroyo LH, Lee RT, Aristizabal O, Turnbull DH, Georgakopoulos D, Kass D, Bond M, et al (1999) Dilated cardiomyopathy in homozygous myosin-binding protein-C mutant mice. J Clin Invest 104: 1235-1244
40. Moolman JA, Reith S, Uhl K, Bailey S, Gautel M, Jeschke B, Fischer C, Ochs J, McKenna WJ, Klues H, et al (2000) A newly created splice donor site in exon 25 of the MyBP-C gene is responsible for inherited hypertrophic cardiomyopathy with incomplete disease penetrance. Circulation 101: 1396-1402
41. Muller OJ, Leuchs B, Pleger ST, Grimm D, Franz WM, Katus HA, Kleinschmidt JA (2006) Improved cardiac gene transfer by transcriptional and transductional targeting of adeno-associated viral vectors. Cardiovasc Res 70: 70-78
42. Olivotto I, Girolami F, Ackerman MJ, Nistri S, Bos JM, Zachara E, Ommen SR, Theis JL, Vaubel RA, Re F, et al (2008) Myofilament protein gene mutation screening and outcome of patients with hypertrophic cardiomyopathy. Mayo Clin Proc 83: 630-638
43. Pohlmann L, Kroger I, Vignier N, Schlossarek S, Kramer E, Coirault C, Sultan KR, El-Armouche A, Winegrad S, Eschenhagen T et al (2007) Cardiac myosin-binding protein C is required for complete relaxation in intact myocytes. Circ Res 101: 928-938
44. Richard P, Charron P, Carrier L, Ledeuil C, Cheav T, Pichereau C, Benaiche A, Isnard R, Dubourg O, Burban M, et al (2003) Hypertrophic cardiomyopathy: distribution of disease genes, spectrum of mutations and implications for molecular diagnosis strategy. Circulation 107: 2227-2232
45. Rottbauer W, Gautel M, Zehelein J, Labeit S, Franz WM, Fischer C, Vollrath B, Mall G, Dietz R, Kubler W, et al (1997) Novel splice donor site mutation in the cardiac myosin-binding protein-C gene in familial hypertrophic cardiomyopathy. Characterization Of cardiac transcript and protein. J Clin Invest 100: 475-482
46. Sadayappan S, Gulick J, Osinska H, Martin LA, Hahn HS, Dorn GW, II, Klevitsky R, Seidman CE, Seidman JG, Robbins J (2005) Cardiac myosin-binding protein-C phosphorylation and cardiac function. Circ Res 97: 1156-1163
47. Sands MS, Barker JE (1999) Percutaneous intravenous injection in neonatal mice. Lab Anim Sci 49: 328-330
48. Sarikas A, Carrier L, Schenke C, Doll D, Flavigny J, Lindenberg KS, Eschenhagen T, Zolk O (2005) Impairment of the ubiquitin-proteasome system by truncated cardiac myosin binding protein C mutants. Cardiovasc Res 66: 33-44
49. Schlossarek S, Mearini G, Carrier L (2011) Cardiac myosin-binding protein C in hypertrophic cardiomyopathy: mechanisms and therapeutic opportunities. J Mol Cell Cardiol 50: 613-620
50. Schlossarek S, Englmann DR, Sultan KR, Sauer M, Eschenhagen T, Carrier L (2012a) Defective proteolytic systems in Mybpc3-targeted mice with cardiac hypertrophy. Basic Res Cardiol 107: 1-13
51. Schlossarek S, Schuermann F, Geertz B, Mearini G, Eschenhagen T, Carrier L (2012b) Adrenergic stress reveals septal hypertrophy and proteasome impairment in heterozygous Mybpc3-targeted knock-in mice. J Muscle Res Cell Motil 33: 5-15
52. Smith PJ, Zhang C, Wang J, Chew SL, Zhang MQ, Krainer AR (2006) An increased specificity score matrix for the prediction of SF2/ASF-specific exonic splicing enhancers. Hum Mol Genet 15: 2490-2508
53. Stefanovic B, Hackl W, Luhrmann R, Schumperli D (1995) Assembly, nuclear import and function of U7 snRNPs studied by microinjection of synthetic U7 RNA into Xenopus oocytes. Nucleic Acids Res 23: 3141-3151
54. van Deutekom JC, Bremmer-Bout M, Janson AA, Ginjaar IB, Baas F, den Dunnen JT, van Ommen GJ (2001) Antisense-induced exon skipping restores dystrophin expression in DMD patient derived muscle cells. Hum Mol Genet 10: 1547-1554
55. van Deutekom JC, Janson AA, Ginjaar IB, Frankhuizen WS, Aartsma-Rus A, Bremmer-Bout M, den Dunnen JT, Koop K, van der Kooi AJ, Goemans NM, et al (2007) Local dystrophin restoration with antisense oligonucleotide PRO051. N Engl J Med 357: 2677-2686
56. van Dijk SJ, Dooijes D, Dos Remedios C, Michels M, Lamers JM, Winegrad S, Schlossarek S, Carrier L, Ten Cate FJ, Stienen GJ, et al (2009) Cardiac myosin-binding protein C mutations and hypertrophic cardiomyopathy. Haploinsufficiency, deranged phosphorylation, and cardiomyocyte dysfunction. Circulation 119: 1473-1483
57. van Dijk SJ, Paalberends ER, Najafi A, Michels M, Sadayappan S, Carrier L, Boontje NM, Kuster DW, van Slegtenhorst M, Dooijes D, et al (2012) Contractile dysfunction irrespective of the mutant protein in human hypertrophic cardiomyopathy with normal systolic function. Circ Heart Fail 5: 36-46
58. Van Driest SL, Vasile VC, Ommen SR, Will ML, Tajik AJ, Gersh BJ, Ackerman MJ (2004) Myosin binding protein C mutations and compound heterozygosity in hypertrophic cardiomyopathy. J Am Coll Cardiol 44: 1903-1910
59. Vignier N, Schlossarek S, Fraysse B, Mearini G, Kramer E, Pointu H, Mougenot N, Guiard J, Reimer R, Hohenberg H, et al (2009) Nonsense-mediated mRNA decay and ubiquitin-proteasome system regulate cardiac myosin-binding protein C mutant levels in cardiomyopathic mice. Circ Res 105: 239-248
60. Vitiello L, Bassi N, Campagnolo P, Zaccariotto E, Occhi G, Malerba A, Pigozzo S, Reggiani C, Ausoni S, Zaglia T, et al (2008) In vivo delivery of naked antisense oligos in aged mdx mice: analysis of dystrophin restoration in skeletal and cardiac muscle. Neuromuscul Disord 18: 597-605
61. Wang Q, Yin H, Camelliti P, Betts C, Moulton H, Lee H, Saleh AF, Gait MJ, Wood MJ (2010) In vitro evaluation of novel antisense oligonucleotides is predictive of in vivo exon skipping activity for Duchenne muscular dystrophy. J Gene Med 12: 354-364