A Cxcl15 Cre Recombinase Mouse Model Useful to Study Gland Development in the Uterus

Area of Science:

• Reproductive biology
• Developmental biology
• Genetics

Background:

• Mammalian uterus contains endometrial glands crucial for pregnancy establishment.
• These glands regulate key processes including blastocyst implantation, decidualization, and placental development.
• Understanding endometrial gland development and function is vital for reproductive health.

Purpose of the Study:

• To develop a novel mouse model for studying uterine glandular epithelium (GE) development and function.
• To investigate the role of Foxa2 in the developing neonatal uterus using a GE-specific Cre recombinase line.

Main Methods:

• Generated a GE-specific Cre recombinase mouse line by inserting iCre into the Cxcl15 gene using CRISPR-Cas9.
• Confirmed specificity of Cxcl15-iCre expression in the developing uterine GE.
• Crossed Cxcl15-iCre mice with floxed Foxa2 mice for conditional gene deletion in GE.

Main Results:

• Cxcl15-iCre expression was confirmed to be specific to the developing uterine GE.
• Conditional deletion of Foxa2 in neonatal GE resulted in adult mice lacking Foxa2 in uterine glands.
• Adult mice with GE-specific Foxa2 deletion were infertile, indicating its critical role in female reproduction.

Conclusions:

• The Cxcl15-iCre mouse line is a valuable tool for studying uterine gland development and function.
• Foxa2 in the uterine GE is essential for fertility and successful pregnancy establishment in mice.
• This model facilitates further research into the mechanisms regulating uterine gland biology.