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
dc.contributor.author | Walton, KD | |
dc.contributor.author | Wagner, KU | |
dc.contributor.author | Rucker, EB | |
dc.contributor.author | Shillingford, JM | |
dc.contributor.author | Miyoshi, K | |
dc.contributor.author | Hennighausen, L | |
dc.coverage.spatial | Ireland | |
dc.date.accessioned | 2023-01-09T19:24:19Z | |
dc.date.available | 2023-01-09T19:24:19Z | |
dc.date.issued | 2001-12-15 | |
dc.identifier.issn | 0925-4773 | |
dc.identifier.issn | 1872-6356 | |
dc.identifier.uri | https://www.ncbi.nlm.nih.gov/pubmed/11731240 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/175384 | en |
dc.description.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. | |
dc.format.medium | ||
dc.language | eng | |
dc.publisher | Elsevier | |
dc.subject | Alleles | |
dc.subject | Animals | |
dc.subject | Apoptosis | |
dc.subject | Blotting, Southern | |
dc.subject | Blotting, Western | |
dc.subject | Cell Differentiation | |
dc.subject | DNA-Binding Proteins | |
dc.subject | Epithelial Cells | |
dc.subject | Female | |
dc.subject | Gene Deletion | |
dc.subject | Genotype | |
dc.subject | Integrases | |
dc.subject | Lactation | |
dc.subject | Mammary Glands, Animal | |
dc.subject | Mice | |
dc.subject | Mice, Inbred C57BL | |
dc.subject | Mice, Knockout | |
dc.subject | Mice, Transgenic | |
dc.subject | Milk Proteins | |
dc.subject | Phenotype | |
dc.subject | Proto-Oncogene Proteins c-bcl-2 | |
dc.subject | RNA | |
dc.subject | Receptors, Prolactin | |
dc.subject | Recombination, Genetic | |
dc.subject | Ribonucleases | |
dc.subject | STAT5 Transcription Factor | |
dc.subject | Spleen | |
dc.subject | Trans-Activators | |
dc.subject | Transgenes | |
dc.subject | Viral Proteins | |
dc.subject | bcl-X Protein | |
dc.title | 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 | |
dc.type | Article | |
dc.identifier.pmid | 11731240 | |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/175384/2/1-s2.0-S0925477301005494-main.pdf | |
dc.identifier.doi | 10.1016/S0925-4773(01)00549-4 | |
dc.identifier.doi | https://dx.doi.org/10.7302/6765 | |
dc.identifier.source | Mechanisms of Development | |
dc.description.version | Published version | |
dc.date.updated | 2023-01-09T19:24:15Z | |
dc.identifier.orcid | 0000-0001-9108-5617 | |
dc.description.filedescription | Description of 1-s2.0-S0925477301005494-main.pdf : Published version | |
dc.identifier.volume | 109 | |
dc.identifier.issue | 2 | |
dc.identifier.startpage | 281 | |
dc.identifier.endpage | 293 | |
dc.identifier.name-orcid | Walton, KD; 0000-0001-9108-5617 | |
dc.identifier.name-orcid | Wagner, KU | |
dc.identifier.name-orcid | Rucker, EB | |
dc.identifier.name-orcid | Shillingford, JM | |
dc.identifier.name-orcid | Miyoshi, K | |
dc.identifier.name-orcid | Hennighausen, L | |
dc.working.doi | 10.7302/6765 | en |
dc.owningcollname | Internal Medicine, Department of |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.