STOCK Pbrm1^{tm1c(EUCOMM)Wtsi}/BrugJ

Stock number: 031875
Product name: Pbrm1^F
Research areas: Cancer Research, Research Tools

Description

Exon 4 of the Pbrm1 (polybromo 1) gene is flanked by loxP sites in this conditional mutant strain. These mice may be useful in studies of renal carcinoma.

Detailed description

This strain was generated using embryonic stem cells provided by the International Knockout Mouse Consortium. Pbrm1 (polybromo 1) encodes BAP180, a component of the SWI/SNF-B chromatin remodeling complex, and functions as a tumor suppressor. Mutations in Pbrm1 are associated with 50% of clear cell renal carcinomas (ccRCC). Exon 4 of the Pbrm1 gene is flanked by loxP sites in this conditional mutant strain. Heterozygous and homozygous mice are healthy, appear normal and are fertile. These mice may be useful in studies of two-hit tumor suppressors and renal cell carcinoma.

When homozygous Pbrm1^F/F mice are combined with a strain expressing Cre recombinase in the kidney, specifically, the parietal cells of Bowman capsule, distal tubules, and collecting ducts (see Stock No. 028196 - Pax8^tm1(cre)Mbu), and a Vhl null allele (for example, Stock No. 012933), resulting offspring exhibit enlarged kidneys, small tumors detectable by 9 months, small, dilated Bowman space, simple cysts and scattered atypical cysts. Mice older than 13 months develop multiple large, homogenous bilateral tumors. Median survival is approximately 12 months of age.

Development

The L1L2_Bact_P cassette was inserted at position 31253749 of Chromosome 14 upstream of exon 4. The cassette is composed of a FRT–flanked lacZ/neomycin sequence followed by a loxP site. A second loxP site is inserted downstream of exon 4 at position 31027895. The construct was introduced into C57BL/6N-derived JM8.F6 embryonic stem (ES) cells and correctly targeted ES cells were injected into blastocysts. Dr. James Brugarolas (The University of Texas Southwestern Medical Center) obtained the resulting chimeric males and bred them to C57BL/6NTac females. Progeny were crossed to mice carrying Gt(ROSA)26Sor^tm1(FLP1)Dym to remove the neomycin cassette. The colony was then bred to mice on an unspecified background. Upon arrival, mice were bred to C57BL/6NJ inbred mice for at least one generation to establish the colony.

Allele

Symbol: Pbrm1^{tm1c(EUCOMM)Wtsi}
Name: targeted mutation 1c, Wellcome Trust Sanger Institute
MGI accession ID: MGI:6120907
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Marker symbol: Pbrm1
Marker name: polybromo 1
Marker synonyms: 2310032M22Rik; 2610016F04Rik; BAF180; PB1; RCC; RGD1565549; SMARCH1
Chromosome: 14
Strain of origin: C57BL/6N
Molecular note: The L1L2_gt0 cassette was inserted at position 30748980 of Chromosome 14 upstream of the critical exon(s) (Build GRCm39). The cassette is composed of an FRT flanked lacZ/neomycin sequence followed by a loxP site. An additional loxP site is inserted downstream of the targeted exon(s) at position 30749852. The critical exon(s) is/are thus flanked by loxP sites. A "conditional ready" (floxed) allele was created by flp recombinase expression in mice carrying this allele to remove the lacZ sequence and neo selection cassette, leaving loxP sites flanking the critical exon(s). Further information on targeting strategies used for this and other IKMC alleles can be found at http://www.informatics.jax.org/mgihome/nomen/IKMC_schematics.shtml.