Alteration in connexin 43 gap junction gene dosage impairs conotruncal heart development

Huang, Grace; Wessels, Andy; Smith, Brian N.; Linask, Kérsti K.; Ewart, Janet; Lo, Cecilia W.

doi:10.1016/s0012-1606(98)80027-4

Cited by 70 publications

(67 citation statements)

References 25 publications

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“…The postpartum lethality of mice with homozygous Cx43 deficiency, observed in mice with a mixed genetic background of 129/Sv-C57BL/6, was delayed for up to 10 days in mice with a CD-1 outbred background (Huang et al, 1998b). Because Cx43 fl/-mice have a mixed 129P2/ OlaHsd-129/Sv-C57BL/6 background and Cx43 del/-mice have a similar mixed background of 129P2/OlaHsd-129/ Sv-C57BL/6-CBA/J, the postpartum lethality of the latter and the survival of the former are the result of differences in Cx43 gene dosage rather than strain background influences.…”

Section: Discussionmentioning

confidence: 99%

Endothelium-specific replacement of the connexin43 coding region by a lacZ reporter gene

Theis

Wit

Schlaeger

et al. 2000

genesis

161

187

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The murine gap junction protein connexin43 (Cx43) is expressed in blood vessels, with vastly different contribution by endothelial and smooth muscle cells. We have used the Cre recombinase under control of TIE2 transcriptional elements to inactivate a floxed Cx43 gene specifically in endothelial cells. Cre-mediated deletion led to replacement of the Cx43 coding region by a lacZ reporter gene. This allowed us to monitor the extent of deletion and to visualize the endothelial expression pattern of Cx43. We found widespread endothelial expression of the Cx43 gene during embryonic development, which became restricted largely to capillaries and small vessels in all adult organs examined. Mice lacking Cx43 in endothelium did not exhibit altered blood pressure, in contrast to mice deficient in Cx40. Our results show that lacZ activation after deletion of the target gene allows us to determine the extent of cell type-specific deletion after phenotypical investigation of the same animal.

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Section: Discussionmentioning

confidence: 99%

Endothelium-specific replacement of the connexin43 coding region by a lacZ reporter gene

Theis

Wit

Schlaeger

et al. 2000

genesis

161

187

View full text Add to dashboard Cite

show abstract

“…Incomplete neural tube closure is possible as well when gap junctions are abnormal [32] and the same damaging mechanism might involve the outflow region of the heart. Targeted knock-out mutants for Cx43 died at birth as a result of a failure in pulmonary gas exchange caused by a swelling and blockage of the right ventricular outflow tract and coronary aneurysms [33][34][35][36][37]. Mutations of Cx43 were found in human fetuses with conotruncal defects like double outlet right ventricle [38].…”

Section: Discussionmentioning

confidence: 99%

Expression of Connexin 43 in the hearts of rat embryos exposed to nitrofen and effects of vitamin A on it

et al. 2005

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Rats with experimental congenital diaphragmatic hernia (CDH) have heart hypoplasia and conotruncal and great vessel malformations that are likely related to disturbed neural crest developmental control. Neural crest cells communicate through intercellular gap junctions whose main protein is Connexin 43 (Cx43). The migration and participation of neural crest cells in heart development is likely influenced by this protein which might be also directly involved in myocardial development. Vitamin A is beneficial for heart hypoplasia in CDH rats. The aims of this study were to examine the status of Cx43 in the heart of embryonal rats exposed to nitrofen and to assess if vitamin A reverts these effects. Pregnant rats received either 100 mg nitrofen or olive oil on E9.5. Each group was divided into two subgroups according to the subsequent treatment with intragastric vitamin A (15,000 i.u.) or vehicle on E10.5 and E11.5. The pups were recovered on E13, E15, and E21 and the hearts were dissected out and pooled. Cx43 mRNA expression was determined by quantitative real-time PCR. Comparisons among groups were made with ANOVA and Bonferroni post hoc tests with a threshold of significance of P<0.05. In control rats Cx43 mRNA was minimally expressed on E13 and E15 and fully expressed on E21. Nitrofen significantly increased Cx43 mRNA on E15. Additional treatment with vitamin A tended to moderate this increase on E15. Cx43 was overexpressed in the hearts of nitrofen-exposed embryonal rats on day E15 of gestation. Vitamin A tended to normalize this expression. The mechanism of action of Cx43 deserves further investigation.

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“…Data from transgenic mice overexpressing a dominantnegative Cx43 chimera or the wild-type protein and from Cx43 null animals are in support of this idea (Lo et al 1999). Whereas mice overexpressing Cx43 show an increase in the migratory activity of cardiac neural crest cells, the absence or functional inhibition by a negativedominant fusion protein leads to a decrease of migration (Ewart et al 1997;Huang et al 1998b). Of note, the perturbation of Cx43 expression also exerts an effect on the proliferation of myocardial cells with an increase in Cx43-overexpressing animals and a decrease in Cx43-deficient mice (Huang et al 1998a,b).…”

Section: Late Prenatal Phase and Migrationmentioning

confidence: 97%

Structure and function of gap junctions in the developing brain

Bruzzone

Dermietzel

2006

Cell Tissue Res

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Gap-junction-dependent neuronal communication is widespread in the developing brain, and the prevalence of gap-junctional coupling is well correlated with specific developmental events. We summarize here our current knowledge of the contribution of gap junctions to brain development and propose that they carry out this role by taking advantage of the full complement of their functional properties. Thus, hemichannel activation may represent a key step in the initiation of Ca(2+) waves that coordinate cell cycle events during early prenatal neurogenesis, whereas both hemichannels and/or gap junctions may control the division and migration of cohorts of precursor cells during late prenatal neurogenesis. Finally, the recent discovery that pannexins, a novel group of proteins prominently expressed in the brain, are able to form both hemichannels and gap-junction channels suggests that we need to seek more than just connexins with respect to these junctions.

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Alteration in connexin 43 gap junction gene dosage impairs conotruncal heart development

Cited by 70 publications

References 25 publications

Endothelium-specific replacement of the connexin43 coding region by a lacZ reporter gene

Endothelium-specific replacement of the connexin43 coding region by a lacZ reporter gene

Expression of Connexin 43 in the hearts of rat embryos exposed to nitrofen and effects of vitamin A on it

Structure and function of gap junctions in the developing brain

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