Phenotype Image Detail

Image

Caption

Combined deletion of Brca2 and Trp53 leads to high-grade prostate intraepithelial neoplasia (HG PIN). (A) Haematoxylin and eosin stained sections of dorsolateral prostate (DLP), ventral prostate (VP) and anterior prostate (AP) of Brca2^tm1Brn/Brca2^tm1Brn Trp53^tm1Brn/Trp53⁺ Tg(Pbsn-cre)4Prb/0 (Brca2^F/F;Trp53^F/+;PBCre4) and Brca2^tm1Brn/Brca2^tm1Brn Trp53^tm1Brn/Trp53^tm1Brn Tg(Pbsn-cre)4Prb/0 (Brca2^F/F;Trp53^F/F;PBCre4) mutants. Homozygous deletion of Brca2 and heterozygous loss of Trp53 (Brca2^F/F;Trp53^F/+;PBCre4) in prostate epithelia results in hyperplasia (indicated with white arrowhead) and PIN (indicated with black arrow). Prostate-specific homozygous deletion of Brca2 and Trp53 (Brca2^F/F;Trp53^F/F;PBCre4) results in hyperplasia (indicated with black arrowhead) and atypical cells at 6 months of age. Close-up in bottom panel shows cluster of atypical cells. Brca2^tm1Brn/Brca2^tm1Brn Trp53^tm1Brn/Trp53^tm1Brn Tg(Pbsn-cre)4Prb/0 mutants have focal HG PIN (indicated with yellow arrows). Black box shows the area that is shown in higher magnification in the panel below. (B) Detail of HG PIN in the AP of the mutants. Left panel shows atypical cells with arrows indicating severe pleomorphic nuclei. Middle panel shows a mitotic figure (black arrowhead), apoptotic body (black arrow) and an area of necrosis (white arrow). Right panel shows epithelial cells protruding into broken-up atypical smooth muscle cells (black arrow) and desmoplastic stroma (black arrowhead).

Copyright

This image is from Francis JC, PLoS Genet 2010;6(6):e1000995, and is displayed under the terms of the Creative Commons Attribution 4.0 International License. J:161511

Associated Alleles

Symbol	Name
Brca2^tm1Brn	breast cancer 2, early onset; targeted mutation 1, Anton Berns
Tg(Pbsn-cre)4Prb	transgene insertion 4, Pradip Roy-Burman
Trp53^tm1Brn	transformation related protein 53; targeted mutation 1, Anton Berns

Associated Genotypes

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