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Published on: January 20, 2022
Normal mammary gland development after MMTV-Cre mediated conditional PAK4 gene depletion
Parisa Rabieifar1, Ting Zhuang1,2, Tânia D F Costa1
1Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
Abstract:
p21-activated kinases (PAKs) are serine/threonine kinases functioning as downstream effectors of the small GTPases Rac1 and Cdc42. Members of the PAK family are overexpressed in human breast cancer, but their role in mammary gland development is not fully explored. Here we examined the functional role of PAK4 in mammary gland development by creating a mouse model of MMTV-Cre driven conditional PAK4 gene depletion in the mammary gland. The PAK4 conditional knock-out mice were born healthy, with no observed developmental deficits. Mammary gland whole-mounts revealed no defects in ductal formation or elongation of the mammary tree through the fat pad. PAK4 gene depletion also did not alter proliferation and invasion of the mammary epithelium in young virgin mice. Moreover, adult mice gave birth to healthy pups with normal body weight upon weaning. This implies that MMTV-Cre induced gene depletion of PAK4 in mice does not impair normal mammary gland development and thereby provides an in vivo model that can be explored for examination of the potential function of PAK4 in breast cancer.
Insights
p21-activated kinases (PAKs) are crucial for cell signaling. PAK4 gene depletion in mice did not affect mammary gland development, suggesting its role in breast cancer warrants further investigation.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- p21-activated kinases (PAKs) are serine/threonine kinases downstream of Rac1 and Cdc42.
- PAK family members are overexpressed in human breast cancer.
- The role of PAKs in mammary gland development is not fully understood.
Purpose of the Study:
- To investigate the functional role of PAK4 in mammary gland development.
- To create a conditional PAK4 knockout mouse model.
Main Methods:
- Developed a mouse model with MMTV-Cre driven conditional PAK4 gene depletion in the mammary gland.
- Analyzed mammary gland development using whole-mounts.
- Assessed mammary epithelium proliferation and invasion in young virgin mice.
- Evaluated reproductive success and pup health.
Main Results:
- PAK4 conditional knockout mice exhibited normal development without observable deficits.
- Mammary gland whole-mounts showed no defects in ductal formation or tree elongation.
- PAK4 depletion did not alter mammary epithelium proliferation or invasion.
- Adult mice successfully reproduced, with healthy pups and normal weaning body weight.
Conclusions:
- Conditional depletion of PAK4 in the mouse mammary gland does not impair normal development.
- This mouse model provides a valuable tool for studying PAK4's potential role in breast cancer.
