Brca1^{L63X /+} rat is a novel model of human BRCA1 deficiency displaying susceptibility to radiation-induced mammary cancer.

ABSTRACT: Women who are heterozygous for deleterious BRCA1 germline mutations harbor a high risk of hereditary breast cancer. Previous Brca1-heterozygous animal models do not recapitulate the breast cancer phenotype, and thus all currently used knockout models adopt conditional, mammary-specific homozygous Brca1 loss or addition of Trp53 deficiency. Herein, we report the creation and characterization of a novel Brca1 mutant rat model harboring the germline L63X mutation, which mimics a founder mutation in Japan, through CRISPR-Cas9-based genome editing. Homozygotes (Brca1^L63X/L63X ) were embryonic lethal, whereas heterozygotes (Brca1^L63X/+ ) showed apparently normal development. Without carcinogen exposure, heterozygotes developed mammary carcinoma at a comparable incidence rat

SUBMITTER: Nakamura Y 

PROVIDER: S-EPMC9530872 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature