The severity of mammary gland developmental defects is linked to the overall functional status of Cx43 as revealed by genetically modified mice

Michael K.G. Stewart, Xiang Qun Gong, Kevin J. Barr, Donglin Bai, Glenn I. Fishman, Dale W. Laird

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Genetically modified mice mimicking ODDD (oculodentodigital dysplasia), a disease characterized by reduced Cx43 (connexin 43)-mediated gap junctional intercellular communication, represent an in vivo model to assess the role of Cx43 in mammary gland development and function. We previously reported that severely compromised Cx43 function delayed mammary gland development and impaired milk ejection in mice that harboured a G60S Cx43 mutant, yet there are no reports of lactation defects in ODDD patients. To address this further, we obtained a second mouse model of ODDD expressing an I130T Cx43 mutant to assess whether a mutant with partial gap junction channel activity would be sufficient to retain mammary gland development and function. The results of the present study show that virgin Cx43I130T/+ mice exhibited a temporary delay in ductal elongation at 4 weeks. In addition, Cx43I130T/+ mice develop smaller mammary glands at parturition due to reduced cell proliferation despite similar overall gland architecture. Distinct from Cx43G60S/+ mice, Cx43I130T/+ mice adequately produce and deliver milk to pups, suggesting that milk ejection is unaffected. Thus the present study suggests that a loss-of-function mutant of Cx43 with partial gap junction channel coupling conductance results in a less severe mammary gland phenotype, which may partially explain the lack of reported lactation defects associated with ODDD patients.

Original languageEnglish
Pages (from-to)401-413
Number of pages13
JournalBiochemical Journal
Volume449
Issue number2
DOIs
StatePublished - 15 Jan 2013
Externally publishedYes

Keywords

  • Connexin 43
  • Development
  • Gap junctional intercellular communication
  • Mammary gland
  • Milk ejection
  • Oculodentodigital dysplasia

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