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Mammary epithelial‐specific knockout of the ephrin‐B2 gene leads to precocious epithelial cell death at lactation
Author(s) -
Weiler Stéphanie,
Rohrbach Valeria,
Pulvirenti Thekla,
Adams Ralf,
Ziemiecki Andrew,
Andres AnneCatherine
Publication year - 2009
Publication title -
development, growth and differentiation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 66
eISSN - 1440-169X
pISSN - 0012-1592
DOI - 10.1111/j.1440-169x.2009.01140.x
Subject(s) - biology , mammary gland , involution (esoterism) , epithelium , ephrin , conditional gene knockout , genetically modified mouse , erythropoietin producing hepatocellular (eph) receptor , microbiology and biotechnology , lactation , knockout mouse , transgene , receptor tyrosine kinase , medicine , endocrinology , morphogenesis , embryonic stem cell , receptor , signal transduction , phenotype , gene , genetics , pregnancy , consciousness , cancer , neuroscience , breast cancer
The family of Eph receptor tyrosine kinases and their membrane bound ligands, the ephrins, are involved in a wide variety of morphogenic processes during embryonic development and adult tissue homeostasis. Receptor‐ligand interaction requires direct cell–cell contact and results in forward and reverse signaling originating from the receptor and ligand, respectively. We have previously shown that EphB4 and ephrinB2 are differentially expressed during the development of the adult mammary parenchyma. Overexpression of EphB4 in the mammary epithelium of transgenic mice leads to perturbations in mammary epithelial morphology, motility and growth. To investigate the role of ephrinB2 signaling in mammary gland biology, we have established transgenic mice exhibiting conditional ephrinB2 knockout in the mammary epithelium. In homozygote double transgenic CreLox mice, specific knockout of ephrinB2 occurred in the mammary epithelium during the first pregnancy‐lactating period. Abolishing ephrinB2 function led to severe interference with the architecture and functioning of the mammary gland at lactation. The morphology of the transgenic lactating glands resembled that of involuting controls, with decreased epithelial cell number and collapsed lobulo‐alveolar structures. Accordingly, massive epithelial cell death and expression of involution‐specific genes were observed. Interestingly, in parallel to cell death, significant cell proliferation was apparent, suggestive of tissue regeneration.