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Generation of Mouse for Conditional Expression of Forkhead Box A2
Peng Wang1, San-Pin Wu2, Kelsey E Brooks1
1Division of Animal Sciences, University of Missouri, Columbia, Missouri.
Endocrinology
|March 17, 2018
Summary
Forkhead box A2 (FOXA2) is crucial for uterine development and pregnancy. A new mouse model shows that conditional FOXA2 loss in adult uteri causes infertility and abnormal development, highlighting its essential role.
Area of Science:
- Reproductive Biology
- Developmental Biology
- Genetics
Background:
- Forkhead box A2 (FOXA2) is a key transcription factor in organogenesis and cancer.
- FOXA2 is vital for uterine function and pregnancy, specifically in endometrial glands.
- Loss of FOXA2 function is linked to human endometrial cancer development.
Purpose of the Study:
- To develop a conditional mouse model for studying mouse FOXA2 (mFOXA2) function in the uterus.
- To investigate the role of FOXA2 in uterine development and fertility using this new model.
Main Methods:
- Generated a conditional mFOXA2 expression system using a minigene at the Rosa26 locus (CAG-S-mFOXA2 allele).
- Utilized Cre-lox recombination by crossing with progesterone receptor (Pgr)-Cre and lactotransferrin (Ltf)-iCre mouse lines for spatiotemporal FOXA2 activation.
- Analyzed FOXA2 protein expression and uterine histology in immature and adult mice.
Main Results:
- Conditional FOXA2 expression in immature Pgr-Cre-CAG-S-mFoxa2 mice showed widespread protein distribution.
- Adult Pgr-Cre-CAG-S-mFoxa2 females exhibited infertility, reduced uterine size, fewer endometrial glands, and abnormal epithelial stratification.
- Adult Ltf-iCre-CAG-S-mFoxa2 mice remained fertile with normal uterine histology, indicating temporal and cell-type-specific effects.
Conclusions:
- The developed conditional mFOXA2 mouse model is effective for studying FOXA2 function.
- Conditional loss of FOXA2 in the adult uterus leads to infertility and significant histological abnormalities.
- This model provides a valuable resource for exploring FOXA2's role in uterine biology and disease.
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