Mammary epithelial-specific knockout of the ephrin-B2 gene leads to precocious epithelial cell death at lactation

Weiler, Stéphanie; Rohrbach, Valeria; Pulvirenti, Thekla; Adams, Ralf; Ziemiecki, Andrew; Andres, Anne-Catherine (2009). Mammary epithelial-specific knockout of the ephrin-B2 gene leads to precocious epithelial cell death at lactation. Development, growth & differentiation, 51(9), pp. 809-19. Richmond (Aus.): Blackwell Publishing Asia 10.1111/j.1440-169X.2009.01140.x

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Unit Tiefenau Hospital [discontinued] > Forschungsgruppe Biologie und Karzinogenese der Brustdrüse [discontinued]

UniBE Contributor:

Rohrbach, Valeria, Ziemiecki, Andrew, Andres, Anne Catherine

ISSN:

0012-1592

Publisher:

Blackwell Publishing Asia

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:13

Last Modified:

05 Dec 2022 14:22

Publisher DOI:

10.1111/j.1440-169X.2009.01140.x

PubMed ID:

19843150

Web of Science ID:

000272192400008

URI:

https://boris.unibe.ch/id/eprint/32336 (FactScience: 197433)

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