The p63 C-terminus is essential for murine oocyte integrity

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2021
Autor:innen
Lena, Anna Maria
Rossi, Valerio
Osterburg, Susanne
Smirnov, Artem
Osterburg, Christian
Tuppi, Marcel
Cappello, Angela
Melino, Gerry
Candi, Eleonora
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Nature communications. Nature Publishing Group. 2021, 12(1), 383. eISSN 2041-1723. Available under: doi: 10.1038/s41467-020-20669-0
Zusammenfassung

The transcription factor p63 mediates distinct cellular responses, primarily regulating epithelial and oocyte biology. In addition to the two amino terminal isoforms, TAp63 and ΔNp63, the 3'-end of p63 mRNA undergoes tissue-specific alternative splicing that leads to several isoforms, including p63α, p63β and p63γ. To investigate in vivo how the different isoforms fulfil distinct functions at the cellular and developmental levels, we developed a mouse model replacing the p63α with p63β by deletion of exon 13 in the Trp63 gene. Here, we report that whereas in two organs physiologically expressing p63α, 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, TAp63β 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 TAp63α-expressing primary oocytes to control cell death in vivo, expanding the current understanding of human primary ovarian insufficiency.

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570 Biowissenschaften, Biologie
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ISO 690LENA, Anna Maria, Valerio ROSSI, Susanne OSTERBURG, Artem SMIRNOV, Christian OSTERBURG, Marcel TUPPI, Angela CAPPELLO, Ivano AMELIO, Gerry MELINO, Eleonora CANDI, 2021. The p63 C-terminus is essential for murine oocyte integrity. In: Nature communications. Nature Publishing Group. 2021, 12(1), 383. eISSN 2041-1723. Available under: doi: 10.1038/s41467-020-20669-0
BibTex
@article{Lena2021Cterm-56499,
  year={2021},
  doi={10.1038/s41467-020-20669-0},
  title={The p63 C-terminus is essential for murine oocyte integrity},
  number={1},
  volume={12},
  journal={Nature communications},
  author={Lena, Anna Maria and Rossi, Valerio and Osterburg, Susanne and Smirnov, Artem and Osterburg, Christian and Tuppi, Marcel and Cappello, Angela and Amelio, Ivano and Melino, Gerry and Candi, Eleonora},
  note={Article Number: 383}
}
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