title: Connexin31 cannot functionally replace connexin43 during cardiac morphogenesis in mice.
abstract: In the gastrulating mouse embryo, the gap junction protein connexin43 is expressed exclusively in cells derived from the inner cell mass, whereas connexin31 is expressed in cells of the trophoblast lineage. Since connexin43 and connexin31 do not form heterotypic gap junction channels in exogenous expression systems, such as HeLa cells and Xenopus oocytes, previous studies have suggested that the incompatibility of these two connexins could contribute to the separation of connexin43-expressing and connexin31-expressing compartments between embryo and extraembryonic tissues at gastrulation, respectively. Thus, we have generated connexin43 knock-in connexin31 mice, in which the coding region of the connexin43 gene was replaced by that of connexin31. Interbreeding of heterozygous connexin43 knock-in connexin31 mice resulted in homozygous connexin43 knock-in connexin31 mice, but none of them survived to adulthood. As these mice were born at the expected Mendelian frequency, we conclude that the reported incompatibility of connexin43 and connexin31 to form heterotypic gap junction channels does not interfere with normal embryonic development. Neonatal homozygous connexin43 knock-in connexin31 hearts showed malformation in the subpulmonary outlet of the right ventricle, similar to general connexin43-deficient mice. Electrocardiograms of neonatal hearts in homozygous connexin43 knock-in connexin31 mice revealed significantly low voltage of the QRS complex. This is in contrast to previous results from our laboratory which showed that replacement of connexin43 by connexin40 resulted in morphologically and functionally normal hearts. We conclude that connexin31 cannot functionally replace connexin43 during cardiac morphogenesis.
authors.affiliation: Institut für Genetik, Universität Bonn, 53117 Bonn, Germany.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Zheng-Fischhöfer
authors.forename: Alexander
authors.initials: A
authors.lastname: Ghanem
authors.forename: Jung-Sun
authors.initials: JS
authors.lastname: Kim
authors.forename: Mark
authors.initials: M
authors.lastname: Kibschull
authors.forename: Gaby
authors.initials: G
authors.lastname: Schwarz
authors.forename: Jörg O
authors.initials: JO
authors.lastname: Schwab
authors.forename: James
authors.initials: J
authors.lastname: Nagy
authors.forename: Elke
authors.initials: E
authors.lastname: Winterhager
authors.forename: Klaus
authors.initials: K
authors.lastname: Tiemann
authors.forename: Klaus
authors.initials: K
authors.lastname: Willecke
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000235:genetics; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism; D017630:Connexins / Q000235:genetics / Q000378:metabolism; D004562:Electrocardiography; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology* / Q000502:physiology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D038081:Organogenesis / Q000235:genetics
chemical_list: D018031:Connexin 43; D017630:Connexins; C068044:GJB3 protein, human