Distinct Brca1 Mutations Differentially Reduce Hematopoietic Stem Cell Function.

ABSTRACT: BRCA1 is a well-known DNA repair pathway component and a tissue-specific tumor suppressor. However, its role in hematopoiesis is uncertain. Here, we report that a cohort of patients heterozygous for BRCA1 mutations experienced more hematopoietic toxicity from chemotherapy than those with BRCA2 mutations. To test whether this reflects a requirement for BRCA1 in hematopoiesis, we generated mice with Brca1 mutations in hematopoietic cells. Mice homozygous for a null Brca1 mutation in the embryonic hematopoietic system (Vav1-iCre;Brca1^{F22-24/F22-24}) developed hematopoietic defects in early adulthood that included reduced hematopoietic stem cells (HSCs). Although mice homozygous for a huBRCA1 knockin allele (Brca1^BRCA1/BRCA1) were normal, mice with a mutant huBRCA1/5382ins

SUBMITTER: Mgbemena VE 

PROVIDER: S-EPMC5267932 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature