Development of thymic lymphomas in mice disrupted of Brca2 allele in the thymus.
Germ-line mutations in BRCA2 predispose to early-onset cancer. Homozygous mutant mouse, which has Brca2 truncated in exon 11 exhibit paradoxic occurrence of growth retardation and development of thymic lymphomas. However, due to its large embryonic lethality, cohort studies on the thymic lymphomas were not feasible. With the aid of Cre-loxP system, we demonstrate here that thymus-specific disruption of Brca2 allele without crossing it to p53-mutant background leads to the development of thymic lymphomas. Varying from 16 weeks to 66 weeks after birth, 25% of mice disrupted of Brca2 in the thymus died of thymic lymphomas, whereas previous report did not observe lymphomagenesis using similar Cre-loxP system. Future analysis of thymic lymphomas from these mice presented here will provide information on the cooperative mutations that are required for the BRCA2-associated pathogenesis of cancer.
Park
Pil-Gu
PG
Research Center for Functional Cellulomics, Department of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea.
Lee
Hyunsook
H
D000818:Animals; D024682:BRCA2 Protein / Q000172:deficiency / Q000235:genetics*; D016516:CD4-CD8 Ratio; D002469:Cell Separation; D005434:Flow Cytometry; D019426:Integrases / Q000235:genetics* / Q000276:immunology; D008223:Lymphoma / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D013953:Thymus Neoplasms / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000276:immunology
D024682:BRCA2 Protein; C106711:BRCA2 protein, mouse; D016159:Tumor Suppressor Protein p53; C045073:Cre recombinase; D019426:Integrases