| First Author | Lena AM | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 383 |
| PubMed ID | 33452256 | Mgi Jnum | J:300878 |
| Mgi Id | MGI:6504748 | Doi | 10.1038/s41467-020-20669-0 |
| Citation | Lena AM, et al. (2021) The p63 C-terminus is essential for murine oocyte integrity. Nat Commun 12(1):383 |
| abstractText | The transcription factor p63 mediates distinct cellular responses, primarily regulating epithelial and oocyte biology. In addition to the two amino terminal isoforms, TAp63 and DeltaNp63, the 3'-end of p63 mRNA undergoes tissue-specific alternative splicing that leads to several isoforms, including p63alpha, p63beta and p63gamma. To investigate in vivo how the different isoforms fulfil distinct functions at the cellular and developmental levels, we developed a mouse model replacing the p63alpha with p63beta by deletion of exon 13 in the Trp63 gene. Here, we report that whereas in two organs physiologically expressing p63alpha, 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, TAp63beta 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 TAp63alpha-expressing primary oocytes to control cell death in vivo, expanding the current understanding of human primary ovarian insufficiency. |
