Mapping Genetic Modifiers of Mammary Tumor Susceptibility in BALB/c-p53+/- Mice
Abstract
The TP53 tumor suppressor gene is critical for inhibiting tumors in many tissues. Heterozygosity at TP53 has been associated with the Li-Fraumeni tumor susceptibility syndrome where breast cancer is the most common tumor in women with this syndrome. We found that the incidence of mammary tumors in mice that were heterozygous for Trp53 varied among strains. Therefore, the mammary tumor-susceptible strain (BALB/cMed) was crossed with a resistant strain (C57BL/6J) to create a panel of 220 backcross mice to allow genetic mapping of chromosomal intervals containing modifiers of mammary tumor susceptibility that varied between these strains. We have monitored tumor type and latency in these mice for >15 months with 50 mice remaining. The incidence of mammary tumors in the Trp53+/- backcross mice was considerably reduced compared to the BALB/c (^6O% vs 30%) confirming the presence of modifier loci in the BALB/c strain that confer susceptibility. We are evaluating linkage of the tumor phenotype to BALB/c polymorphisms in the Ink4a and Prdkc genes that result in proteins that have reduced activity in cell cycle checkpoint and DNA repair activities. We have also established the mechanism by which the wild type allele of Trp53 is lost during mammary tumor formation in these mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2001
- Accession Number
- ADB274518
Entities
People
- Anneke C. Blackburn
- D. J. Jerry
Organizations
- University of Massachusetts Amherst