Medulloblastomas Initiated by Homologous Recombination Defects in Mice.

ABSTRACT: Germline mutations of homologous-recombination (HR) genes are among the top contributors to medulloblastomas. A significant portion of human medulloblastomas exhibit genomic signatures of HR defects. Whether ablation of Brca2 and Palb2, and their related Brca1 and Bccip genes, in the mouse brain can differentially initiate medulloblastomas was explored here. Conditional knockout mouse models of these HR genes and a conditional knockdown of Bccip (shBccip-KD) were established. Deletion of any of these genes led to microcephaly and neurologic defects, with Brca1^- and Bccip^- producing the worst defects. Trp53 co-deletion significantly rescued the microcephaly with Brca1, Palb2, and Brca2 deficiency but exhibited limited impact on Bccip^- mice. For the first tim

SUBMITTER: Lu H 

PROVIDER: S-EPMC11816638 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature