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Updated: Jul 8, 2026

Evaluation of Mammary Gland Development and Function in Mouse Models
Published on: July 21, 2011
Lactation failure in Src knockout mice is due to impaired secretory activation
Harriet Watkin1, Monica M Richert, Andrew Lewis
1Department of Pathology, University of Colorado Health Sciences Center, Research Complex I, South Tower, Mail Stop 8104, 12801 East 17th Avenue, Aurora, CO 80045, USA. harriet.watkin@uchsc.edu
Background:
Mammary gland development culminates in lactation and is orchestrated by numerous stimuli and signaling pathways. The Src family of nonreceptor tyrosine kinases plays a pivotal role in cell signaling. In order to determine if Src plays a role in mammary gland development we have examined mammary gland development and function during pregnancy and lactation in mice in which expression of Src has been eliminated.
Results:
We have characterized a lactation defect in the Src-/- mice which results in the death of over 80% of the litters nursed by Src-/- dams. Mammary gland development during pregnancy appears normal in these mice; however secretory activation does not seem to occur. Serum prolactin levels are normal in Src-/- mice compared to wildtype controls. Expression of the prolactin receptor at both the RNA and protein level was decreased in Src-/- mice following the transition from pregnancy to lactation, as was phosphorylation of STAT5 and expression of milk protein genes. These results suggest that secretory activation, which occurs following parturition, does not occur completely in Src-/- mice. Failed secretory activation results in precocious involution in the mammary glands of Src-/- even when pups were suckling. Involution was accelerated following pup withdrawal perhaps as a result of incomplete secretory activation. In vitro differentiation of mammary epithelial cells from Src-/- mice resulted in diminished production of milk proteins compared to the amount of milk proteins produced by Src+/+ cells, indicating a direct role for Src in regulating the transcription/translation of milk protein genes in mammary epithelial cells.
Conclusion:
Src is an essential signaling modulator in mammary gland development as Src-/- mice exhibit a block in secretory activation that results in lactation failure and precocious involution. Src appears to be required for increased expression of the prolactin receptor and successful downstream signaling, and alveolar cell organization.
Insights
The Src tyrosine kinase is essential for successful lactation. Mice lacking Src show impaired mammary gland development, leading to lactation failure and early tissue regression, highlighting Src's role in milk production.
Area of Science:
- Cellular signaling
- Developmental biology
- Biochemistry
Background:
- Mammary gland development is crucial for lactation, involving complex signaling pathways.
- Src family kinases are key regulators of intracellular signaling.
- The role of Src in mammary gland development and lactation remained unclear.
Purpose of the Study:
- To investigate the role of Src in mammary gland development and function.
- To determine the impact of Src deficiency on pregnancy and lactation in mice.
Main Methods:
- Generation and analysis of Src-deficient (Src-/-) mice.
- Assessment of mammary gland development, lactation, and involution.
- Analysis of prolactin receptor expression, STAT5 phosphorylation, and milk protein gene expression.
Main Results:
- Src-/- mice exhibited severe lactation defects, with over 80% of litters dying.
- Mammary gland development during pregnancy was normal, but secretory activation failed post-partum.
- Reduced prolactin receptor expression, STAT5 phosphorylation, and milk protein production were observed in Src-/- mice.
- Src deficiency led to precocious mammary gland involution, even during suckling.
Conclusions:
- Src is essential for secretory activation during lactation.
- Src signaling is required for proper prolactin receptor expression and downstream signaling.
- Src plays a critical role in mammary gland development, lactation, and preventing premature involution.
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