The p63 C-terminus is essential for murine oocyte integrity.

ABSTRACT: The transcription factor p63 mediates distinct cellular responses, primarily regulating epithelial and oocyte biology. In addition to the two amino terminal isoforms, TAp63 and ?Np63, the 3'-end of p63 mRNA undergoes tissue-specific alternative splicing that leads to several isoforms, including p63?, p63? and p63?. 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? with p63? by deletion of exon 13 in the Trp63 gene. Here, we report that whereas in two organs physiologically expressing p63?, 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? 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?-expressing primary oocytes to control cell death in vivo, expanding the current understanding of human primary ovarian insufficiency.

SUBMITTER: Lena AM 

PROVIDER: S-EPMC7810856 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature