Stat5a is mandatory for adult mammary gland development and lactogenesis.
Abstract
Prolactin (PRL) induces mammary gland development (defined as mammopoiesis) and lactogenesis. Binding of PRL to its receptor leads to the phosphorylation and activation of STAT (signal transducers and activators of transcription) proteins, which in turn promote the expression of specific genes. The activity pattern of two STAT proteins, Stat5a and Stat5b, in mammary tissue during pregnancy suggests an active role for these transcription factors in epithelial cell differentiation and milk protein gene expression. To investigate the function of Stat5a in mammopoiesis and lactogenesis we disrupted this gene in mice by gene targeting. Stat5a-deficient mice developed normally and were indistinguishable from hemizygous and wild-type littermates in size, weight, and fertility. However, mammary lobuloalveolar outgrowth during pregnancy was curtailed, and females failed to lactate after parturition because of a failure of terminal differentiation. Although Stat5b has a 96% similarity with Stat5a and a superimposable expression pattern during mammary gland development it failed to counterbalance for the absence of Stat5a. These results document that Stat5a is the principal and an obligate mediator of mammopoietic and lactogenic signaling.
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All of the other STAT knock-outs have relatively mild phenotypes correlated with rather specific defects in response to certain cytokines or growth factors.
“All of the other STAT knock-outs have relatively mild phenotypes correlated with rather specific defects in response to certain cytokines or growth factors (12”
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- Authors
- Liu, X., Robinson, G. W., Wagner, K. U., Garrett, L., Wynshaw-Boris, A., & Hennighausen, L.
- Affiliations
- National Institutes of Health (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1997-01-15
- Volume
- 11
- Issue
- 2
- Pages
- 179-186
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2147028876
- Cited by
- 1,111
- References
- 0
- Citations by year
- 2026: 8 · 2025: 19 · 2024: 11 · 2023: 22 · 2022: 20 · 2021: 15 · 2020: 28 · 2019: 23 · 2018: 16 · 2017: 24 · 2016: 29 · 2015: 24 · 2014: 44 · 2013: 33 · 2012: 40
- Type
- posted content
- Language
- en
- Open access
- closed
- Locations
- Genes & Development (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- STAT5A, STAT5B, mammary gland development, lactogenesis, prolactin signaling, terminal differentiation, milk protein gene expression, gene targeting, transcription factors
- MeSH terms
- Animals, Cell Differentiation, DNA-Binding Proteins, Female, Homozygote, Lactation, Male, Mammary Glands, Animal, Mice, Inbred C57BL, Mice, Inbred Strains, Milk Proteins, Pregnancy, Trans-Activators, Gene Targeting, Gene Expression Regulation, Developmental, STAT5 Transcription Factor, Mice
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