The p63 C-terminus is essential for murine oocyte integrity

The transcription factor p63 mediates distinct cellular responses, primarily regulating epithelial and oocyte biology. In addition to the two amino terminal isoforms, TAp63 and Delta Np63, the 3'-end of p63 mRNA undergoes tissue-specific alternative splicing that leads to several isoforms, including p63 alpha, p63 beta and p63 gamma. To investigate in vivo how the different isoforms fulfil distinct functions at the cellular and developmental levels, we developed a mouse model replacing the p63 alpha with p63 beta by deletion of exon 13 in the Trp63 gene. Here, we report that whereas in two organs physiologically expressing p63 alpha, such as thymus and skin, no abnormalities are detected, total infertility is evident in heterozygous female mice. A sharp reduction in the number of primary oocytes during the first week after birth occurs as a consequence of the enhanced expression of the pro-apoptotic transcriptional targets Puma and Noxa by the tetrameric, constitutively active, TAp63 beta isoform. Hence, these mice show a condition of ovary dysfunction, resembling human primary ovary insufficiency. Our results show that the p63 C-terminus is essential in TAp63 alpha -expressing primary oocytes to control cell death in vivo, expanding the current understanding of human primary ovarian insufficiency. The transcription factor p63 mediates different cellular responses affecting epithelial and oocyte biology. Here, the authors generate a mouse model (HET Delta 13p63 mice) expressing the p63 beta isoform and show this affects ovary development, phenocopying a human syndrome, primary ovary insufficiency.

Automated summary

The transcription factor p63 plays a crucial role in regulating cellular responses related to epithelial and oocyte biology. By replacing p63 alpha with p63 beta in a mouse model, researchers demonstrated that this change affects ovary development, mimicking the characteristics of human primary ovary insufficiency.