Phenotype Image Detail

Image

Caption

Brca2^tm1Brn/Brca2^tm1Brn Trp53^tm1Brn/Trp53^tm1BrnTg(Pbsn-cre)4Prb/0 (Brca2^F/F;Trp53^F/F;PBCre4) prostates have hallmarks of cancer. (A) Ki-67 immunohistochemistry shows increased proliferation in areas of low-grade prostate intraepithelial neoplasia (LG PIN) in Brca2^tm1Brn/Brca2^tm1Brn Tg(Pbsn-cre)4Prb/0 (Brca2^F/F;PBCre4) and Brca2^tm1Brn/Brca2^tm1Brn Trp53^tm1Brn/Trp53⁺ Tg(Pbsn-cre)4Prb/0 (Brca2^F/F;Trp53^F/+;PBCre4) prostates, a low number of proliferating cells are present in control (Brca2^F/F) prostates. Brca2^tm1Brn/Brca2^tm1Brn Trp53^tm1Brn/Trp53^tm1Brn Tg(Pbsn-cre)4Prb/0 mutants have a large number of proliferating cells in areas of high-grade (HG) PIN. (B) Androgen receptor (AR) immunohistochemistry demonstrating increased levels of expression throughout the nucleus and cytoplasm in areas of LG PIN in Brca2^tm1Brn/Brca2^tm1Brn Tg(Pbsn-cre)4Prb/0 and Brca2^tm1Brn/Brca2^tm1Brn Trp53^tm1Brn/Trp53⁺ Tg(Pbsn-cre)4Prb/0 prostates, compared to control prostates. Brca2^tm1Brn/Brca2^tm1Brn Trp53^tm1Brn/Trp53^tm1Brn Tg(Pbsn-cre)4Prb/0 have increased AR expression predominantly in the nucleus of cells in areas of HG PIN. (C) p63 immunohistochemistry shows an increase in p63-expressing cells in HG PIN lesions in Brca2^tm1Brn/Brca2^tm1Brn Trp53^tm1Brn/Trp53^tm1Brn Tg(Pbsn-cre)4Prb/0 prostates and normal expression in the basal cells of control (Brca2^F/F;Trp53^F/F) prostates. Arrows indicate a cluster of abnormal p63-expressing cells that are rounder and nearer the lumen. (D) Panel shows p63 (red) and CK5 (green) fluorescent immunohistochemistry analysis with labelled cells protruding into the lumen (white arrowheads) in a region of PIN in Brca2^tm1Brn/Brca2^tm1Brn Trp53^tm1Brn/Trp53^tm1Brn Tg(Pbsn-cre)4Prb/0 mutants. (E) Panel shows CK5 (green, basal cells) and CK8 (red, luminal cells) fluorescent immunohistochemistry with PIN lesions in Brca2^tm1Brn/Brca2^tm1Brn Trp53^tm1Brn/Trp53^tm1Brn Tg(Pbsn-cre)4Prb/0 mutants displaying an increase in luminal cells next to clusters of basal cells. White arrowhead marks CK5 and CK8 double-labelled cells. DAPI nuclear stain is blue. The anterior prostates of 16-month-old animals are shown.

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 Tg(Pbsn-cre)4Prb/0	involves: 129P2/OlaHsd * C57BL/6 * DBA/2
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