Slow progressive conduction and contraction defects in loss of Nkx2-5 mice after cardiomyocyte terminal differentiation

Laboratory Investigation

Volumn 89, Issue 9, 2009, Pages 983-993

  Takeda, Morihiko ^a   Briggs, Laura E ^a   Wakimoto, Hiroko ^b   Marks, Melissa H ^a   Warren, Sonisha A ^a   Lu, Jonathan T ^c   Weinberg, Ellen O ^d   Robertson, Keith D ^a   Chien, Kenneth R ^e   Kasahara, Hideko ^a  

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

^b TOKYO MEDICAL AND DENTAL UNIVERSITY   (Japan)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d BOSTON UNIVERSITY MEDICAL CENTER   (United States)

^e MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

Cardiomyocyte; Conduction defects; Gene targeting; Hypertrophy; Nkx2 5

Indexed keywords

CRE RECOMBINASE; GLYCERALDEHYDE 3 PHOSPHATE DEHYDROGENASE; TAMOXIFEN; TRANSCRIPTION FACTOR NKX2.5;

ALLELE; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ATRIOVENTRICULAR BLOCK; CARDIOMEGALY; CELL CYCLE; CELL DIFFERENTIATION; CHROMATIN STRUCTURE; CONGENITAL HEART MALFORMATION; CONTROLLED STUDY; CRE GENE; DISEASE COURSE; GENE MUTATION; HEART CONDUCTION; HEART CONTRACTION; HEART LEFT VENTRICLE FAILURE; HEART MUSCLE CELL; HEART MUSCLE CONDUCTION DISTURBANCE; MOUSE; NKX2 5 GENE; NONHUMAN; PERINATAL PERIOD; PHENOTYPE; PRIORITY JOURNAL; TRANSGENE;

ANIMALS; CARDIOMEGALY; CARDIOMYOPATHIES; CELL DIFFERENTIATION; DOWN-REGULATION; ELECTROCARDIOGRAPHY; FEMALE; HEART CONDUCTION SYSTEM; HOMEODOMAIN PROTEINS; MALE; MICE; MICE, KNOCKOUT; MYOCARDIAL CONTRACTION; MYOCYTES, CARDIAC; TELEMETRY; TRANSCRIPTION FACTORS;

EID: 69349086498     PISSN: 00236837     EISSN: 15300307     Source Type: Journal    
DOI: 10.1038/labinvest.2009.59     Document Type: Article

References (35)

1. Harvey RP. NK-2 homeobox genes and heart development. Dev Biol 1996;178:203-216.
2. Harvey RP, Rosenthal N. Heart Development. Academic Press: San Diego, CA, USA, 1999.
3. Lints TJ, Parsons LM, Hartley L, et al. Nkx-2.5: a novel murine homeobox gene expressed in early heart progenitor cells and their myogenic descendants. Development 1993;119:419-431.
4. Komuro I, Izumo S. Csx: a murine homeobox-containing gene specifically expressed in the developing heart. Proc Natl Acad Sci USA 1993;90:8145-8149.
5. Kasahara H, Bartunkova S, Schinke M, et al. Cardiac and extracardiac expression of Csx/Nkx2.5 homeodomain protein. Circ Res 1998;82:936-946.
6. Lyons I, Parsons LM, Hartley L, et al. Myogenic and morphogenetic defects in the heart tubes of murine embryos lacking the homeo box gene Nkx2-5. Genes Dev 1995;9:1654-1666.
7. Tanaka M, Chen Z, Bartunkova S, et al. The cardiac homeobox gene Csx/Nkx2.5 lies genetically upstream of multiple genes essential for heart development. Development 1999;126:1269-1280.
8. Pashmforoush M, Lu JT, Chen H, et al. 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.
9. Schott JJ, Benson DW, Basson CT, et al. Congenital heart disease caused by mutations in the transcription factor NKX2-5. Science 1998;281:108-111.
10. Benson DW, Silberbach GM, Kavanaugh-McHugh A, et al. Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways. J Clin Invest 1999;104:1567-1573.
11. 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.
12. Konig K, Will JC, Berger F, et al. Familial congenital heart disease, progressive atrioventricular block and the cardiac homeobox transcription factor gene NKX2.5: identification of a novel mutation. Clin Res Cardiol 2006;95:499-503.
13. Sachinidis A, Fleischmann BK, Kolossov E, et al. Cardiac specific differentiation of mouse embryonic stem cells. Cardiovasc Res 2003;58:278-291.
14. Puceat M. Rb and LEK1: a 'pas de deux' in cardiogenesis. Cell Cycle 2005;4:1030-1032.
15. Briggs LE, Takeda M, Cuadra AE, et al. Perinatal loss of Nkx2-5 results in rapid conduction and contraction defects. Circ Res 2008;103:580-590.
16. Chan JY, Takeda M, Briggs LE, et al. Identification of cardiac-specific myosin light chain kinase. Circ Res 2008;102:571-580.
17. Anversa P, Leri A, Kajstura J. Cardiac regeneration. J Am Coll Cardiol 2006;47:1769-1776.
18. Ahuja P, Sdek P, MacLellan WR. Cardiac myocyte cell cycle control in development, disease, and regeneration. Physiol Rev 2007;87:521-544.
19. Oberdoerffer P, Sinclair DA. The role of nuclear architecture in genomic instability and ageing. Nat Rev Mol Cell Biol 2007;8:692-702.
20. Rowat AC, Lammerding J, Herrmann H, et al. Towards an integrated understanding of the structure and mechanics of the cell nucleus. Bioessays 2008;30:226-236.
21. Hayashi S, McMahon AP. Efficient recombination in diverse tissues by a tamoxifen-inducible form of Cre: a tool for temporally regulated gene activation/inactivation in the mouse. Dev Biol 2002;244:305-318.
22. Wakimoto H, Kasahara H, Maguire CT, et al. Developmentally modulated cardiac conduction failure in transgenic mice with fetal or postnatal overexpression of DNA nonbinding mutant Nkx2.5. J Cardiovasc Electrophysiol 2002;13:682-688.
23. Scherrer-Crosbie M, Ullrich R, Bloch KD, et al. Endothelial nitric oxide synthase limits left ventricular remodeling after myocardial infarction in mice. Circulation 2001;104:1286-1291.
24. Janssens S, Pokreisz P, Schoonjans L, et al. Cardiomyocyte-specific overexpression of nitric oxide synthase 3 improves left ventricular performance and reduces compensatory hypertrophy after myocardial infarction. Circ Res 2004;94:1256-1262.
25. Minhas KM, Saraiva RM, Schuleri KH, et al. Xanthine oxidoreductase inhibition causes reverse remodeling in rats with dilated cardiomyopathy. Circ Res 2006;98:271-279.
26. Biben C, Weber R, Kesteven S, et al. Cardiac septal and valvular dysmorphogenesis in mice heterozygous for mutations in the homeobox gene Nkx2-5. Circ Res 2000;87:888-895.
27. Tanaka M, Berul CI, Ishii M, et al. 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.
28. Jay PY, Harris BS, Maguire CT, et al. Nkx2-5 mutation causes anatomic hypoplasia of the cardiac conduction system. J Clin Invest 2004;113:1130-1137.
29. Moskowitz IP, Kim JB, Moore ML, et al. A molecular pathway including Id2, Tbx5, and Nkx2-5 required for cardiac conduction system development. Cell 2007;129:1365-1376.
30. Sedmera D, Pexieder T, Vuillemin M, et al. Developmental patterning of the myocardium. Anat Rec 2000;258:319-337.
31. Parlakian A, Charvet C, Escoubet B, et al. Temporally controlled onset of dilated cardiomyopathy through disruption of the SRF gene in adult heart. Circulation 2005;112:2930-2939.
32. Thompson JT, Rackley MS, O'Brien TX. Upregulation of the cardiac homeobox gene Nkx2-5 (CSX) in feline right ventricular pressure overload. Am J Physiol 1998;274(5 Part 2):H1569-H1573.
33. Saadane N, Alpert L, Chalifour LE. Expression of immediate early genes, GATA-4, and Nkx-2.5 in adrenergic-induced cardiac hypertrophy and during regression in adult mice. Br J Pharmacol 1999;127:1165-1176.
34. Bar H, Kreuzer J, Cojoc A, et al. Upregulation of embryonic transcription factors in right ventricular hypertrophy. Basic Res Cardiol 2003;98:285-294.
35. Oka T, Xu J, Molkentin JD. Re-employment of developmental transcription factors in adult heart disease. Semin Cell Dev Biol 2007;18:117-131.