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The severity of mammary gland developmental defects is linked to the overall functional status of Cx43 as revealed by genetically modified mice.
Biochem J. 2013 Jan 15; 449(2):401-13.BJ

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.

Authors+Show Affiliations

Department of Physiology and Pharmacology, Western University, London, ON, Canada N6A 5C1.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23075222

Citation

Stewart, Michael K G., et al. "The Severity of Mammary Gland Developmental Defects Is Linked to the Overall Functional Status of Cx43 as Revealed By Genetically Modified Mice." The Biochemical Journal, vol. 449, no. 2, 2013, pp. 401-13.
Stewart MK, Gong XQ, Barr KJ, et al. The severity of mammary gland developmental defects is linked to the overall functional status of Cx43 as revealed by genetically modified mice. Biochem J. 2013;449(2):401-13.
Stewart, M. K., Gong, X. Q., Barr, K. J., Bai, D., Fishman, G. I., & Laird, D. W. (2013). The severity of mammary gland developmental defects is linked to the overall functional status of Cx43 as revealed by genetically modified mice. The Biochemical Journal, 449(2), 401-13. https://doi.org/10.1042/BJ20121070
Stewart MK, et al. The Severity of Mammary Gland Developmental Defects Is Linked to the Overall Functional Status of Cx43 as Revealed By Genetically Modified Mice. Biochem J. 2013 Jan 15;449(2):401-13. PubMed PMID: 23075222.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The severity of mammary gland developmental defects is linked to the overall functional status of Cx43 as revealed by genetically modified mice. AU - Stewart,Michael K G, AU - Gong,Xiang-Qun, AU - Barr,Kevin J, AU - Bai,Donglin, AU - Fishman,Glenn I, AU - Laird,Dale W, PY - 2012/10/19/entrez PY - 2012/10/19/pubmed PY - 2013/3/30/medline SP - 401 EP - 13 JF - The Biochemical journal JO - Biochem. J. VL - 449 IS - 2 N2 - 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. SN - 1470-8728 UR - https://www.unboundmedicine.com/medline/citation/23075222/The_severity_of_mammary_gland_developmental_defects_is_linked_to_the_overall_functional_status_of_Cx43_as_revealed_by_genetically_modified_mice_ L2 - https://portlandpress.com/biochemj/article-lookup/doi/10.1042/BJ20121070 DB - PRIME DP - Unbound Medicine ER -