Evaluating the role of connexin43 in congenital heart disease: Screening for mutations in patients with outflow tract anomalies and the analysis of knock-in mouse models

Journal of Cardiovascular Disease Research

Volumn 2, Issue 4, 2011, Pages 206-212

  Huang, Guo Ying ^a,c   Xie, Li Jian ^a   Linask, Kaari ^b   Zhang, Chen ^a   Zhao, Xiao Qing ^a,b   Yang, Yi ^a   Zhou, Guo Min ^d   Wu, Ying Jie ^b   Marquez Rosado, Lucrecia ^g   McElhinney, Doff ^e,h   Goldmuntz, Elizabeth ^e   Liu, Chengyu ^f   Lampe, Paul ^g   Chatterjee, Bishwanath ^b,i   Lo, Cecilia ^b,i  

^a CHILDREN S HOSPITAL OF FUDAN UNIVERSITY   (China)

^b Lab of Developmental Neurobiology   (United States)

^c FUDAN UNIVERSITY   (China)

^d FUDAN UNIVERSITY   (China)

^e UNIVERSITY OF PENNSYLVANIA   (United States)

^f NATIONAL INSTITUTES OF HEALTH   (United States)

^g Fred Hutchinson Cancer Research Center   (United States)

^h BOSTON CHILDREN S HOSPITAL   (United States)

ⁱ UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

congenital heart disease; Connexin43; gap junction; knock in mouse model; outflow tract; phosphorylations

Indexed keywords

CASEIN KINASE; CONNEXIN 43; DNA; PROTEIN KINASE C;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ATRIOVENTRICULAR SEPTAL DEFECT; CHILD; CONGENITAL HEART DISEASE; CONTROLLED STUDY; DNA SEQUENCE; ENZYME PHOSPHORYLATION; FALLOT TETRALOGY; FEMALE; GENE; GENE FUNCTION; GENETIC SCREENING; GJA1 GENE; HUMAN; INFANT; KNOCKOUT GENE; MALE; MOLECULAR PATHOLOGY; MOUSE; NONHUMAN; NUCLEIC ACID BASE SUBSTITUTION; OUTFLOW TRACT ANOMALY; POINT MUTATION; PRESCHOOL CHILD; PRIORITY JOURNAL; PROTEIN TRANSPORT; VALVULAR HEART DISEASE;

EID: 81755161340     PISSN: 09753583     EISSN: 09762833     Source Type: Journal    
DOI: 10.4103/0975-3583.89804     Document Type: Article

References (32)

1. Severs N. Cardiac muscle cell interaction: From microanatomy to the molecular make-up of the gap junction. Histol Histopathol 1995;10:481-501.
2. Severs N. Cardiovascular disease. Novartis Found Symp 1999;219:188-206; discussion 206-11.
3. Reaume A, de Sousa P, Kulkarni S, Langille B, Zhu D, Davies T, et al. Cardiac malformation in neonatal mice lacking connexin43. Science 1995;267:1831-4.
4. Li W, Waldo K, Linask K, Chen T, Wessels A, Parmacek M, et al. An essential role for connexin43 gap junctions in mouse coronary artery development. Development 2002;129:2031-42. (Pubitemid 34874217)
5. Walker D, Vacha S, Kirby M, Lo C. Connexin43 deficiency causes dysregulation of coronary vasculogenesis. Dev Biol 2005;284:479-98. (Pubitemid 41188150)
6. Lo C, Waldo K, Kirby M. Gap junction communication and the modulation of cardiac neural crest cells. Trends Cardiovasc Med 1999;9:63-9. (Pubitemid 29512238)
7. Hutson M, Kirby M. Model systems for the study of heart development and disease. Cardiac neural crest and conotruncal malformations. Semin Cell Dev Biol 2007;18:101-10. (Pubitemid 46343796)
8. Ewart J, Cohen M, Meyer R, Huang G, Wessels A, Gourdie R, et al. Heart and neural tube defects in transgenic mice overexpressing the cx43 gap junction gene. Development 1997;124:1281-92. (Pubitemid 27190101)
9. Huang G, Wessels A, Smith B, Linask K, Ewart J, Lo C. Alteration in connexin 43 gap junction gene dosage impairs conotruncal heart development. Dev Biol 1998;198:32-44. (Pubitemid 28272700)
10. Levin M, Mercola M. Gap junctions are involved in the early generation of left-right asymmetry. Dev Biol 1998;203:90-105. (Pubitemid 28506665)
11. Levin M, Mercola M. Gap junction-mediated transfer of left-right patterning signals in the early chick blastoderm is upstream of shh asymmetry in the node. Development 1999;126:4703-14.
12. Le M, Li Z, Cilley R, Donahue H, Chinoy M. Connexin 43 gene expression in mice with cardiopulmonary developmental defects. Front Biosci 2006;11:3014-25. (Pubitemid 43800393)
13. Rhee D, Zhao X, Francis R, Huang G, Mably J, Lo C. Connexin 43 regulates epicardial cell polarity and migration in coronary vascular development. Development 2009;136:3185-93.
14. Britz-Cunningham S, Shah M, Zuppan C, Fletcher W. Mutations of the connexin43 gap-junction gene in patients with heart malformations and defects of laterality. N Engl J Med 1995;332:1323-9.
15. Dasgupta C, Martinez A, Zuppan C, Shah M, Bailey L, Fletcher W. Identification of connexin43 (alpha1) gap junction gene mutations in patients with hypoplastic left heart syndrome by denaturing gradient gel electrophoresis (dgge). Mutat Res 2001;479:173-86. (Pubitemid 32695499)
16. Gebbia M, Towbin J, Casey B. Failure to detect connexin43 mutations in 38 cases of sporadic and familial heterotaxy. Circulation 1996;94:1909-12. (Pubitemid 26349304)
17. Debrus S, Tuffery S, Matsuoka R, Galal O, Sarda P, Sauer U, et al. Lack of evidence for connexin 43 gene mutations in human autosomal recessive lateralization defects. J Mol Cell Cardiol 1997;29:1423-31. (Pubitemid 27259655)
18. Splitt M, Burn J, Goodship J. Connexin43 mutations in sporadic and familial defects of laterality. N Engl J Med 1995;333:941.
19. Penman Splitt M, Tsai M, Burn J, Goodship J. Absence of mutations in the regulatory domain of the gap junction protein connexin 43 in patients with visceroatrial heterotaxy. Heart 1997;77:369-70. (Pubitemid 27208180)
20. De Luca A, Sarkozy A, Consoli F, De Zorzi A, Mingarelli R, Digilio M, et al. Exclusion of cx43 gene mutation as a major cause of criss-cross heart anomaly in man. Int J Cardiol 2010;144:300-2.
21. Lampe P, TenBroek E, Burt J, Kurata W, Johnson R, Lau A. Phosphorylation of connexin43 on serine368 by protein kinase c regulates gap junctional communication. J Cell Biol 2000;149:1503-12. (Pubitemid 30437622)
22. Cooper C, Lampe P. Casein kinase 1 regulates connexin-43 gap junction assembly. J Biol Chem 2002;277:44962-8. (Pubitemid 36159094)
23. Lampe P, Cooper C, King T, Burt J. Analysis of Cx43 phosphorylated at S325, S328, S330 in nomixic and ischemic heart. J Cell Sci 2006;119:3435-42. (Pubitemid 44405227)
24. Fishman G, Eddy R, Shows T, Rosenthal L, Leinwand L. The human connexin gene family of gap junction proteins: Distinct chromosomal locations but similar structures. Genomics 1991;10:250-6.
25. Sosinsky G, Solan J, Gaietta G, Ngan L, Lee G, Mackey M, et al. The C-terminus of connexin43 adopts different conformations in the Golgi and gap junction as detected with structure-specific antibodies. Biochem J 2007;408:375-85.
26. King T, Gurley K, Prunty J, Shin J, Kemp C, Lampe P. Deficiency in the gap junction protein connexin32 alters p27kip1 tumor suppression and mapk activation in a tissue-specific manner. Oncogene 2005;24:1718-26. (Pubitemid 40461128)
27. Moreno A, Fishman G, Spray D. Phosphorylation shifts unitary conductance and modifies voltage dependent kinetics of human connexin43 gap junction channels. Biophys J 1992;62:51-3.
28. Lampe P, TenBroek E, Burt J, Kurata W, Johnson R, Lau A. Phosphorylation of connexin43 on serine368 by protein kinase C regulates gap junctional communication. J Cell Biol 2000;149:1503-12. (Pubitemid 30437622)
29. Ek-Vitorin J, King T, Heyman N, Lampe P, Burt J. Selectivity of connexin 43 channels is regulated through protein kinase C-dependent phosphorylation. Circ Res 2006;98:1498-505. (Pubitemid 44297072)
30. Solan J, Fry M, TenBroek E, Lampe P. Connexin43 phosphorylation at S368 is acute during S and G2/M and in response to protein kinase C activation. J Cell Sci 2003;116:2203-11. (Pubitemid 36722367)
31. Paznekas W, Boyadjiev S, Shapiro R, Daniels O, Wollnik B, Keegan C, et al. Connexin 43 (gja1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia. Am J Hum Genet 2003;72:408-18. (Pubitemid 36194249)
32. Flenniken A, Osborne L, Anderson N, Ciliberti N, Fleming C, Gittens J, et al. A gja1 missense mutation in a mouse model of oculodentodigital dysplasia. Development2005;132:4375-86. (Pubitemid 41576698)