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ID 114214
Author
Walton, Katherine D. National Institutes of Health
Wagner, Kay-Uwe National Institutes of Health|University of Nebraska Medical Center
Rucker III, Edmund B. National Institutes of Health|University of Missouri
Shillingford, Jonathan M. National Institutes of Health
Hennighausen, Lothar National Institutes of Health
Keywords
Conditional gene deletion
Mammary gland
Epithelium
Bcl-x
Bax
Apoptosis
Involution
Cre-recombinase
Content Type
Journal Article
Description
In the mammary gland Bcl-x is the most abundant cell survival factor from the Bcl-2 family. Since Bcl-x null mice die around day 12 of embryogenesis, the relevance of this protein in organ development and function is poorly understood. In erythroid cells bcl-x gene expression is controlled by cytokines and the transcription factor Stat5 (signal transducer and activator of transcription). However, we identified that bcl-x RNA levels in mammary tissue from prolactin receptor- and Stat5-null mice were indistinguishable from wild type mice. We have proposed that Bcl-x might control the survival of mammary epithelial cells throughout pregnancy, lactation, and the early stages of involution, and we have now tested this hypothesis through the conditional deletion of the bcl-x gene from mouse mammary epithelium. Conditional (floxed) bcl-x alleles were excised from alveolar cells during pregnancy using a Cre transgene under the control of the whey acidic protein gene promoter. Deletion of the bcl-x gene from the entire epithelial compartment (ducts and alveoli) was achieved by expressing Cre-recombinase under control of the mouse mammary tumor virus long terminal repeat. The absence of Bcl-x did not compromise proliferation and differentiation of mammary ductal and alveolar epithelial cells in virgin mice and during pregnancy and lactation. However, epithelial cell death and tissue remodeling were accelerated in the bcl-x conditional knockout mice during the first stage of involution. Concomitant deletion of the bax gene did not significantly modify the Bcl-x phenotype. Our results suggest that Bcl-x is not essential during mammopoiesis, but is critical for controlled apoptosis during the first phase of involution. Published by Elsevier Science Ireland Ltd.
Journal Title
Mechanisms of Development
ISSN
09254773
NCID
AA10790903
AA11536507
Publisher
Elsevier
Volume
109
Issue
2
Start Page
281
End Page
293
Published Date
2001-09-27
Rights
Open Archive
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Oral Sciences