Phenotypes Associated with This Genotype

Genotype
MGI:4819193

• Allelic Composition: Brca2^tm1Brn/Brca2^tm1Brn; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

High-grade prostate intraepithelial neoplasia in Brca2^tm1Brn/Brca2^tm1Brn Tg(Pbsn-cre)4Prb/0 Trp53^tm1Brn/Trp53^tm1Brn and prostate hyperplasia and intraepithelial neoplasia in Brca2^tm1Brn/Brca2^tm1Brn Trp53^tm1Brn/Trp53⁺ Tg(Pbsn-cre)4Prb/0 mice

neoplasm

increased prostate intraepithelial neoplasia incidence ( J:161511 )

♂ • by 10 - 14 months of age both focal low grade and high grade PIN are seen

♂ • the incidence of high grade PIN is increased in mutant mice homozygous for the Trp53 allele relative to mice heterozygous for the Trp53 allele

♂ • frequently multiple ducts of each lobe have high grade PIN, which are present in proximal and distal regions of the prostate and consist of many atypical cells filling the lumen

♂ • high grade PIN lesions are predominantly seen in the anterior and dorsal prostate

♂ • levels of cell proliferation are 30 fold higher in PIN lesions

♂ • high grade PIN lesions frequently contain large groups of basal cells some of which are rounder in shape and positioned near the lumen

♂ • high grade lesions continue to proliferate post castration

reproductive system

prostate gland hyperplasia ( J:161511 )

♂ • focal hyperplasia is seen beginning as early as 6 months of age

increased prostate intraepithelial neoplasia incidence ( J:161511 )

♂ • by 10 - 14 months of age both focal low grade and high grade PIN are seen

♂ • the incidence of high grade PIN is increased in mutant mice homozygous for the Trp53 allele relative to mice heterozygous for the Trp53 allele

♂ • frequently multiple ducts of each lobe have high grade PIN, which are present in proximal and distal regions of the prostate and consist of many atypical cells filling the lumen

♂ • high grade PIN lesions are predominantly seen in the anterior and dorsal prostate

♂ • levels of cell proliferation are 30 fold higher in PIN lesions

♂ • high grade PIN lesions frequently contain large groups of basal cells some of which are rounder in shape and positioned near the lumen

♂ • high grade lesions continue to proliferate post castration

abnormal prostate gland physiology ( J:161511 )

♂ • areas of hyperplasia are positive for markers of DNA damage

♂ • 20 fold increase in apoptotic cells in areas of high grade PIN

endocrine/exocrine glands

prostate gland hyperplasia ( J:161511 )

♂ • focal hyperplasia is seen beginning as early as 6 months of age

increased prostate intraepithelial neoplasia incidence ( J:161511 )

♂ • by 10 - 14 months of age both focal low grade and high grade PIN are seen

♂ • the incidence of high grade PIN is increased in mutant mice homozygous for the Trp53 allele relative to mice heterozygous for the Trp53 allele

♂ • frequently multiple ducts of each lobe have high grade PIN, which are present in proximal and distal regions of the prostate and consist of many atypical cells filling the lumen

♂ • high grade PIN lesions are predominantly seen in the anterior and dorsal prostate

♂ • levels of cell proliferation are 30 fold higher in PIN lesions

♂ • high grade PIN lesions frequently contain large groups of basal cells some of which are rounder in shape and positioned near the lumen

♂ • high grade lesions continue to proliferate post castration

abnormal prostate gland physiology ( J:161511 )

♂ • areas of hyperplasia are positive for markers of DNA damage

♂ • 20 fold increase in apoptotic cells in areas of high grade PIN

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
prostate cancer		DOID:10283	OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959	J:161511