A mouse model of human congenital heart disease high incidence of diverse cardiac anomalies and ventricular noncompaction produced by heterozygous Nkx2-5 homeodomain missense mutation

Circulation: Cardiovascular Genetics

Volumn 7, Issue 4, 2014, Pages 423-433

  Ashraf, Hassan ^a   Pradhan, Lagnajeet ^b   Chang, Eileen I ^a   Terada, Ryota ^a   Ryan, Nicole J ^a   Briggs, Laura E ^a   Chowdhury, Rajib ^a   Zárate, Miguel A ^a   Sugi, Yukiko ^c   Nam, Hyun Joo ^b   Benson, D Woodrow ^d   Anderson, Robert H ^e   Kasahara, Hideko ^a  

^a UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^b The University of Texas at Dallas   (United States)

^c MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^d MEDICAL COLLEGE OF WISCONSIN   (United States)

^e NEWCASTLE UNIVERSITY   (United Kingdom)

Author keywords

Congenital; Genetics

Indexed keywords

DOUBLE STRANDED DNA; TRANSCRIPTION FACTOR NKX2.5; HOMEODOMAIN PROTEIN; NKX2-5 PROTEIN, MOUSE; TRANSCRIPTION FACTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ATRIOVENTRICULAR SEPTAL DEFECT; CONGENITAL HEART MALFORMATION; CONTROLLED STUDY; CRYSTAL STRUCTURE; DNA BINDING; EBSTEIN ANOMALY; GEL MOBILITY SHIFT ASSAY; GROWTH RETARDATION; HEART VENTRICLE SEPTUM DEFECT; HEART VENTRICLE WALL; HETEROZYGOTE; INCIDENCE; MISSENSE MUTATION; MOUSE; MOUSE MODEL; NONHUMAN; NONSENSE MUTATION; PENETRANCE; PHENOTYPE; PRIORITY JOURNAL; PROTEIN DNA BINDING; PROTEIN PROTEIN INTERACTION; PROTEIN STABILITY; SOMATIC MUTATION; TRICUSPID VALVE; VENTRICULAR NONCOMPACTION; AMINO ACID SEQUENCE; ANIMAL; C57BL MOUSE; DISEASE MODEL; GENE TARGETING; GENETICS; HEART VENTRICLE; HUMAN; KNOCKOUT MOUSE; MOLECULAR GENETICS; PATHOLOGY; PROTEIN TERTIARY STRUCTURE; TRANSGENIC MOUSE;

MURINAE; MUS;

AMINO ACID SEQUENCE; ANIMALS; DISEASE MODELS, ANIMAL; GENE KNOCK-IN TECHNIQUES; HEART DEFECTS, CONGENITAL; HEART VENTRICLES; HETEROZYGOTE; HOMEODOMAIN PROTEINS; HUMANS; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MICE, TRANSGENIC; MOLECULAR SEQUENCE DATA; MUTATION, MISSENSE; PHENOTYPE; PROTEIN STRUCTURE, TERTIARY; TRANSCRIPTION FACTORS;

EID: 84925969711     PISSN: 1942325X     EISSN: 19423268     Source Type: Journal    
DOI: 10.1161/CIRCGENETICS.113.000281     Document Type: Article

References (52)

1. Hoffman JI, Kaplan S, Liberthson RR. Prevalence of congenital heart disease. Am Heart J. 2004;147:425-439
2. Capozzi G, Caputo S, Pizzuti R, Martina L, Santoro M, Santoro G, Sarubbi B, lacono C, D'Alto M, Bigazzi MC, Pacileo G, Merlino E, Caianiello G, Russo MG, Calabrò R. Congenital heart disease in live-born children: Incidence, distribution, and yearly changes in the Campania Region. J Cardiovasc Med (Hagerstown). 2008;9:368-374
3. Dolk H, Loane M, Garne E; European Surveillance of Congenital Anomalies (EUROCAT) Working Group. Congenital heart defects in Europe: Prevalence and perinatal mortality, 2000 to 2005. Circulation. 2011;123:841-849
4. van der Bom T, Zomer AC, Zwinderman AH, Meijboom FJ, Bouma BJ, Mulder BJ. The changing epidemiology of congenital heart disease. Nat Rev Cardiol. 2011;8:50-60
5. Roybal JL, Santore MT, Flake AW. Stem cell and genetic therapies for the fetus. Semin Fetal Neonatal Med. 2010;15:46-51
6. Benson DW. Genetic origins of pediatric heart disease. Pediatr Cardiol. 2010;31:422-429
7. Andelfinger G. Genetic factors in congenital heart malformation. Clin Genet. 2008;73:516-527
8. Benson DW, Silberbach GM, Kavanaugh-McHugh A, Cottrill C, Zhang Y, Riggs S, Smalls O, Johnson MC, Watson MS, Seidman JG, Seidman CE, Plowden J, Kugler JD. Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways. J Clin Invest. 1999;104:1567-1573
9. Reamon-Buettner SM, Borlak J. NKX2-5: An update on this hypermutable homeodomain protein and its role in human congenital heart disease (CHD). Hum Mutat. 2010;31:1185-1194
10. Stallmeyer B, Fenge H, Nowak-Göttl U, Schulze-Bahr E. Mutational spectrum in the cardiac transcription factor gene NKX2.5 (CSX) associated with congenital heart disease. Clin Genet. 2010;78:533-540
11. De Luca A, Sarkozy A, Consoli F, Ferese R, Guida V, Dentici ML, Mingarelli R, Bellacchio E, Tuo G, Limongelli G, Digilio MC, Marino B, Dallapiccola B. Familial transposition of the great arteries caused by multiple mutations in laterality genes. Heart. 2010;96:673-677
12. Liu XY, Wang J, Yang YQ, Zhang YY, Chen XZ, Zhang W, Wang XZ, Zheng JH, Chen YH. Novel NKX2-5 mutations in patients with familial atrial septal defects. Pediatr Cardiol. 2011;32:193-201
13. Wang J, Liu XY, Yang YQ. Novel NKX2-5 mutations responsible for congenital heart disease. Genet Mol Res. 2011;10:2905-2915
14. Kasahara H, Lee B, Schott JJ, Benson DW, Seidman JG, Seidman CE, Izumo S. Loss of function and inhibitory effects of human CSX/NKX2.5 homeoprotein mutations associated with congenital heart disease. J Clin Invest. 2000;106:299-308
15. Kasahara H, Benson DW. Biochemical analyses of eight NKX2.5 homeodomain missense mutations causing atrioventricular block and cardiac anomalies. Cardiovasc Res. 2004;64:40-51
16. Hacking DF. 'Knock, and it shall be opened': knocking out and knocking in to reveal mechanisms of disease and novel therapies. Early Hum Dev. 2008;84:821-827
17. Biben C, Weber R, Kesteven S, Stanley E, McDonald L, Elliott DA, Barnett L, Köentgen F, Robb L, Feneley M, Harvey RP. Cardiac septal and valvular dysmorphogenesis in mice heterozygous for mutations in the homeobox gene Nkx2-5. Circ Res. 2000;87:888-895
18. Tanaka M, Berul CI, Ishii M, Jay PY, Wakimoto H, Douglas P, Yamasaki N, Kawamoto T, Gehrmann J, Maguire CT, Schinke M, Seidman CE, Seidman JG, Kurachi Y, Izumo S. A mouse model of congenital heart disease: Cardiac arrhythmias and atrial septal defect caused by haploinsufficiency of the cardiac transcription factor Csx/Nkx2.5. Cold Spring Harb Symp Quant Biol. 2002;67:317-325
19. Winston JB, Erlich JM, Green CA, Aluko A, Kaiser KA, Takematsu M, Barlow RS, Sureka AO, LaPage MJ, Janss LL, Jay PY. Heterogeneity of genetic modifiers ensures normal cardiac development. Circulation. 2010;121:1313-1321
20. Grow MW, Krieg PA. Tinman function is essential for vertebrate heart development: Elimination of cardiac differentiation by dominant inhibitory mutants of the tinman-related genes, XNkx2-3 and XNkx2-5. Dev Biol. 1998;204:187-196
21. Kasahara H, Wakimoto H, Liu M, Maguire CT, Converso KL, Shioi T, Huang WY, Manning WJ, Paul D, Lawitts J, Berul CI, Izumo S. Progressive atrioventricular conduction defects and heart failure in mice expressing a mutant Csx/Nkx2.5 homeoprotein. J Clin Invest. 2001;108:189-201
22. Pradhan L, Genis C, Scone P, Weinberg EO, Kasahara H, Nam HJ. Crystal structure of the human NKX2.5 homeodomain in complex with DNA target. Biochemistry. 2012;51:6312-6319
23. Pashmforoush M, Lu JT, Chen H, Amand TS, Kondo R, Pradervand S, Evans SM, Clark B, Feramisco JR, Giles W, Ho SY, Benson DW, Silberbach M, Shou W,Chien KR. Nkx2-5 pathways and congenital heart disease; loss of ventricular myocyte lineage specification leads to progressive cardiomyopathy and complete heart block. Cell. 2004;117:373-386
24. Briggs LE, Takeda M, Cuadra AE, Wakimoto H, Marks MH, Walker AJ, Seki T, Oh SP, Lu JT, Sumners C, Raizada MK, Horikoshi N, Weinberg EO, Yasui K, Ikeda Y, Chien KR, Kasahara H. Perinatal loss of Nkx2-5 results in rapid conduction and contraction defects. Circ Res. 2008;103:580-590
25. Warren SA, Terada R, Briggs LE, Cole-Jeffrey CT, Chien WM, Seki T, Weinberg EO, Yang TP, Chin MT, Bungert J, Kasahara H. Differential role of Nkx2-5 in activation of the atrial natriuretic factor gene in the developing versus failing heart. Mol Cell Biol. 2011;31:4633-4645
26. Kasahara H, Bartunkova S, Schinke M, Tanaka M, Izumo S. Cardiac and extracardiac expression of Csx/Nkx2.5 homeodomain protein. Circ Res. 1998;82:936-946
27. Terada R, Warren S, Lu JT, Chien KR, Wessels A, Kasahara H. Ablation of Nkx2-5 at mid-embryonic stage results in premature lethality and cardiac malformation. Cardiovasc Res. 2011;91:289-299
28. Reamon-Buettner SM, Borlak J. Somatic NKX2-5 mutations as a novel mechanism of disease in complex congenital heart disease. J Med Genet. 2004;41:684-690
29. Jenni R, Oechslin E, Schneider J, Attenhofer Jost C, Kaufmann PA. Echocardiographic and pathoanatomical characteristics of isolated left ventricular non-compaction: A step towards classification as a distinct cardiomyopathy. Heart. 2001;86:666-671
30. Savolainen SM, Foley JF, Elmore SA. Histology atlas of the developing mouse heart with emphasis on E11.5 to E18.5. Toxicol Pathol. 2009;37:395-414
31. Paterick TE, Umland MM, Jan MF, Ammar KA, Kramer C, Khandheria BK, Seward JB, Tajik AJ. Left ventricular noncompaction: A 25-year odyssey. J Am Soc Echocardiogr. 2012;25:363-375
32. Soto B, Becker AE, Moulaert AJ, Lie JT, Anderson RH. Classification of ventricular septal defects. Br Heart J. 1980;43:332-343
33. Minette MS, Sahn DJ. Ventricular septal defects. Circulation. 2006;114:2190-2197
34. Jay PY, Harris BS, Maguire CT, Buerger A, Wakimoto H, Tanaka M, Kupershmidt S, Roden DM, Schultheiss TM, O'Brien TX, Gourdie RG, Berul CI, Izumo S. Nkx2-5 mutation causes anatomic hypoplasia of the cardiac conduction system. J Clin Invest. 2004;113:1130-1137
35. Anderson RH, Brown NA, Webb S. Development and structure of the atrial septum. Heart. 2002;88:104-110
36. Cole-Jeffrey CT, Terada R, Neth MR, Wessels A, Kasahara H. Progressive anatomical closure of foramen ovale in normal neonatal mouse hearts. Anat Rec (Hoboken). 2012;295:764-768
37. Tanaka M, Chen Z, Bartunkova S, Yamasaki N, Izumo S. The cardiac homeobox gene Csx/Nkx2.5 lies genetically upstream of multiple genes essential for heart development. Development. 1999;126:1269-1280
38. Jay PY, Rozhitskaya O, Tarnavski O, Sherwood MC, Dorfman AL, Lu Y, Ueyama T, Izumo S. Haploinsufficiency of the cardiac transcription factor Nkx2-5 variably affects the expression of putative target genes. FASEB J. 2005;19:1495-1497
39. Zambrano E, Marshalko SJ, Jaffe CC, Hui P. Isolated noncompaction of the ventricular myocardium: Clinical and molecular aspects of a rare cardiomyopathy. Lab Invest. 2002;82:117-122
40. Sinkovec M, Kozelj M, Podnar T. Familial biventricular myocardial noncompaction associated with Ebstein's malformation. Int J Cardiol. 2005;102:297-302
41. Freedom RM, Yoo SJ, Perrin D, Taylor G, Petersen S, Anderson RH. The morphological spectrum of ventricular noncompaction. Cardiol Young. 2005;15:345-364
42. Sedmera D, Pexieder T, Vuillemin M, Thompson RP, Anderson RH. Developmental patterning of the myocardium. Anat Rec. 2000;258:319-337
43. Lamers WH, Virágh S, Wessels A, Moorman AF, Anderson RH. Formation of the tricuspid valve in the human heart. Circulation. 1995;91:111-121
44. de Lange FJ, Moorman AF, Anderson RH, Männer J, Soufan AT, de Gierde Vries C, Schneider MD, Webb S, van den Hoff MJ, Christoffels VM. Lineage and morphogenetic analysis of the cardiac valves. Circ Res. 2004;95:645-654
45. de Vlaming A, Sauls K, Hajdu Z, Visconti RP, Mehesz AN, Levine RA, Slaugenhaupt SA, Hagège A, Chester AH, Markwald RR, Norris RA. Atrioventricular valve development: New perspectives on an old theme. Differentiation. 2012;84:103-116
46. Wu B, Baldwin HS, Zhou B. Nfatc1 directs the endocardial progenitor cells to make heart valve primordium. Trends Cardiovasc Med. 2013;23:294-300
47. Attenhofer Jost CH, Connolly HM, O'Leary PW, Warnes CA, Tajik AJ, Seward JB. Left heart lesions in patients with Ebstein anomaly. Mayo Clin Proc. 2005;80:361-368
48. Habets PE, Moorman AF, Clout DE, van Roon MA, Lingbeek M, van Lohuizen M, Campione M, Christoffels VM. Cooperative action of Tbx2 and Nkx2.5 inhibits ANF expression in the atrioventricular canal: Implications for cardiac chamber formation. Genes Dev. 2002;16:1234-1246
49. Thattaliyath BD, Firulli BA, Firulli AB. The basic-helix-loop-helix transcription factor HAND2 directly regulates transcription of the atrial naturetic peptide gene. J Mol Cell Cardiol. 2002;34:1335-1344
50. Stennard FA, Costa MW, Elliott DA, Rankin S, Haast SJ, Lai D, Mc-Donald LP, Niederreither K, Dolle P, Bruneau BG, Zorn AM, Harvey RP. Cardiac T-box factor Tbx20 directly interacts with Nkx2-5, GATA4, and GATA5 in regulation of gene expression in the developing heart. Dev Biol. 2003;262:206-224
51. Akazawa H, Kudoh S, Mochizuki N, Takekoshi N, Takano H, Nagai T, Komuro I. A novel LIM protein Cal promotes cardiac differentiation by association with CSX/NKX2-5. J Cell Biol. 2004;164:395-405
52. Yuasa S, Onizuka T, Shimoji K, Ohno Y, Kageyama T, Yoon SH, Egashira T, Seki T, Hashimoto H, Nishiyama T, Kaneda R, Murata M, Hattori F, Makino S, Sano M, Ogawa S, Prall OW, Harvey RP, Fukuda K. Zac1 is an essential transcription factor for cardiac morphogenesis. Circ Res. 2010;106:1083-1091.