Conditional deletion of the bcl-x gene from mouse mammary epithelium results in accelerated apoptosis during involution but does not compromise cell function during lactation

Katherine D. Walton, Kay Uwe Wagner, Edmund B. Rucker, Jonathan M. Shillingford, Keiko Miyoshi, Lothar Hennighausen

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)281-293
Number of pages13
JournalMechanisms of Development
Volume109
Issue number2
DOIs
StatePublished - Dec 15 2001

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Lactation
Breast
Epithelium
Apoptosis
Alveolar Epithelial Cells
Genes
Pregnancy
Epithelial Cells
Prolactin Receptors
Mouse mammary tumor virus
Erythroid Cells
Terminal Repeat Sequences
Gene Deletion
Human Mammary Glands
Transducers
Transgenes
Knockout Mice
Embryonic Development
Cell Survival
Cell Death

Keywords

  • Apoptosis
  • Bax
  • Bcl-x
  • Conditional gene deletion
  • Cre-recombinase
  • Epithelium
  • Involution
  • Mammary gland

ASJC Scopus subject areas

  • Embryology
  • Developmental Biology

Cite this

Conditional deletion of the bcl-x gene from mouse mammary epithelium results in accelerated apoptosis during involution but does not compromise cell function during lactation. / Walton, Katherine D.; Wagner, Kay Uwe; Rucker, Edmund B.; Shillingford, Jonathan M.; Miyoshi, Keiko; Hennighausen, Lothar.

In: Mechanisms of Development, Vol. 109, No. 2, 15.12.2001, p. 281-293.

Research output: Contribution to journalArticle

Walton, Katherine D. ; Wagner, Kay Uwe ; Rucker, Edmund B. ; Shillingford, Jonathan M. ; Miyoshi, Keiko ; Hennighausen, Lothar. / Conditional deletion of the bcl-x gene from mouse mammary epithelium results in accelerated apoptosis during involution but does not compromise cell function during lactation. In: Mechanisms of Development. 2001 ; Vol. 109, No. 2. pp. 281-293.
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