Cardiomyocyte-specific deletion of the coxsackievirus and adenovirus receptor results in hyperplasia of the embryonic left ventricle and abnormalities of sinuatrial valves

Jin Wen Chen, Bin Zhou, Qian Chun Yu, Sangyoon J. Shin, Kai Jiao, Michael D. Schneider, H. Scott Baldwin, Jeffrey M. Bergelson

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

The coxsackievirus and adenovirus receptor (CAR), which mediates infection by the viruses most commonly associated with myocarditis, is a transmembrane component of specialized intercellular junctions, including the myocardial intercalated disc; it is known to mediate cell-cell recognition, but its natural function is poorly understood. We used conditional gene targeting to investigate the possible functions of CAR during embryonic development, generating mice with both germline and tissue-specific defects in CAR expression. Homozygous germline deletion of CAR exon 2 or cardiomyocyte-specific gene deletion at embryonic day 10 (E10) mediated by Cre recombinase expressed under the control of the cardiac troponin T promoter resulted in death by E12.5; embryos showed marked cardiac abnormalities by E10.5, with hyperplasia of the left ventricular myocardium, distention of the cardinal veins, and abnormalities of sinuatrial valves. Within the hyperplastic left ventricle, increased numbers of proliferating cells were evident; persistent expression of N-myc in the hyperplastic myocardium and attenuated expression of the trabecular markers atrial natriuretic factor and bone morphogenic protein 10 indicated that proliferating cardiomyocytes had failed to differentiate and form normal trabeculae. In electron micrographs, individual CAR-deficient cardiomyocytes within the left ventricle appeared normal, but intercellular junctions were ill-formed or absent, consistent with the known function of CAR as a junctional molecule; myofibrils were also poorly organized. When cardiomyocyte-specific deletion occurred somewhat later (by E11, mediated by Cre under control of the α-myosin heavy chain promoter), animals survived to adulthood and did not have evident cardiac abnormalities. These results indicate that during a specific temporal window, CAR expression on cardiomyocytes is essential for normal cardiac development. In addition, the results suggest that CAR-mediated intercellular contacts may regulate proliferation and differentiation of cardiomyocytes within the embryonic left ventricular wall.

Original languageEnglish (US)
Pages (from-to)923-930
Number of pages8
JournalCirculation Research
Volume98
Issue number7
DOIs
StatePublished - Apr 2006
Externally publishedYes

Fingerprint

Enterovirus
Cardiac Myocytes
Heart Ventricles
Hyperplasia
Intercellular Junctions
Myocardium
Embryo Loss
Troponin T
Gene Targeting
Myosin Heavy Chains
adenovirus receptor
Myofibrils
Myocarditis
Gene Deletion
Atrial Natriuretic Factor
Virus Diseases
Embryonic Development
Veins
Exons
Cell Count

Keywords

  • Adhesion molecules
  • Cardiac development
  • Cardiomyopathy
  • Coxsackievirus receptor
  • Hyperplasia
  • Intercellular junctions
  • Mouse heart development

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Cardiomyocyte-specific deletion of the coxsackievirus and adenovirus receptor results in hyperplasia of the embryonic left ventricle and abnormalities of sinuatrial valves. / Chen, Jin Wen; Zhou, Bin; Yu, Qian Chun; Shin, Sangyoon J.; Jiao, Kai; Schneider, Michael D.; Baldwin, H. Scott; Bergelson, Jeffrey M.

In: Circulation Research, Vol. 98, No. 7, 04.2006, p. 923-930.

Research output: Contribution to journalArticle

Chen, Jin Wen ; Zhou, Bin ; Yu, Qian Chun ; Shin, Sangyoon J. ; Jiao, Kai ; Schneider, Michael D. ; Baldwin, H. Scott ; Bergelson, Jeffrey M. / Cardiomyocyte-specific deletion of the coxsackievirus and adenovirus receptor results in hyperplasia of the embryonic left ventricle and abnormalities of sinuatrial valves. In: Circulation Research. 2006 ; Vol. 98, No. 7. pp. 923-930.
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AU - Zhou, Bin

AU - Yu, Qian Chun

AU - Shin, Sangyoon J.

AU - Jiao, Kai

AU - Schneider, Michael D.

AU - Baldwin, H. Scott

AU - Bergelson, Jeffrey M.

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