Heart and head defects in mice lacking pairs of connexins

Alex Simon, Andrea R. McWhorter, Julie A. Dones, Charity L. Jackson, Hwu Dau Rw Chen

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Gene ablation studies in mice have revealed roles for gap junction proteins (connexins) in heart development. Of the 20 connexins in vertebrates, four are expressed in developing heart: connexin37 (Cx37), connexin40 (Cx40), connexin43 (Cx43), and connexin45 (Cx45). Although each cardiac connexin has a different pattern of expression, some heart cells coexpress multiple connexins during cardiac morphogenesis. Since different connexins could have overlapping functions, some developmental phenotypes may only become evident when more than one connexin is ablated. In this study, we interbred Cx40-/- and Cx43-/- mice to generate mice lacking both Cx40 and Cx43. Cx40 -/-Cx43-/- mice die around embryonic day 12.5 (E12.5), much earlier than either Cx40-/- or Cx43-/- mice, and they exhibit malformed hearts with ventricles that are abnormally rotated, suggesting a looping defect. Some Cx40-/-Cx43-/- animals also develop head defects characteristic of exencephaly. In addition, we examined mice lacking both Cx40 and Cx37 and found a high incidence of atrial and ventricular septal defects at birth. These results provide further evidence for the importance of gap junctions in embryonic development. Moreover, ablating different pairs of cardiac connexins results in distinct heart defects, suggesting both common and unique functions for Cx40, Cx43, and Cx37 during cardiac morphogenesis.

Original languageEnglish (US)
Pages (from-to)369-383
Number of pages15
JournalDevelopmental Biology
Volume265
Issue number2
DOIs
StatePublished - Jan 15 2004

Fingerprint

Connexins
Connexin 43
Head
Morphogenesis
Neural Tube Defects
Atrial Heart Septal Defects
Gap Junctions
Ventricular Heart Septal Defects
Heart Ventricles
Embryonic Development
Vertebrates
Parturition
Phenotype
Incidence

Keywords

  • Cardiac development
  • Cardiac malformation
  • Connexin
  • Cx37
  • Cx40
  • Cx43
  • Exencephaly
  • Gap junction
  • Intercellular communication

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Heart and head defects in mice lacking pairs of connexins. / Simon, Alex; McWhorter, Andrea R.; Dones, Julie A.; Jackson, Charity L.; Chen, Hwu Dau Rw.

In: Developmental Biology, Vol. 265, No. 2, 15.01.2004, p. 369-383.

Research output: Contribution to journalArticle

Simon, Alex ; McWhorter, Andrea R. ; Dones, Julie A. ; Jackson, Charity L. ; Chen, Hwu Dau Rw. / Heart and head defects in mice lacking pairs of connexins. In: Developmental Biology. 2004 ; Vol. 265, No. 2. pp. 369-383.
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