Pms-2 Knockout Mouse
OHSU # 0417
Mutations in the DNA mismatch repair pathway have been shown to be involved in the development of certain cancers. PMS2 is one of the genes involved in the DNA mismatch/repair pathway. PMS2 knock-out mice and cell lines provide a novel model to study cancer and could potentially aid in the development of new therapeutics for oncology. Licensing and collaborative research opportunities exist with respect to these biological materials.
PMS2 protein is part of a repair complex that includes MLH1. Phenotype of the mice suggest that this gene might be involved in a relevant mechanism for tumorigenesis.
PMS2-deficient mouse tissues show increased spontaneous mutations throughout their genomes. In contrast to the situation with MLH1, two of the three germline mutations described may be dominant negative mutations in humans.
There is a striking increase in the tumor incidence- particularly lymphomas and sarcomas (>80% of the mice have tumors after 1 year as compared with control mice where <5% have tumors). PMS2 mutant cells are more resistant to DNA alkylating agents.
1. Drug screening for tumorcidal drugs. Use cells to screen for drugs that target mismatch repair deficient (-/-) cells. These drugs could be used for specifically killing mismatch repair defective tumors in vivo without damaging normal tissues. Can use +/+ and +/- cells for controls and mice for in vivo proof of concept.
2. Disease model system. Disease model for people carrying germline mutation in PMS2, some of whom develop HNPCC and other human cancers.
3. Model system for effect of diet in a cancer predisposing background. Allow studies on how diet and/or other drugs affect the development of cancer in Pms2 mutation carriers (+/-). Also, provide a system to test new and existing drugs for their ability to slow diet-provoked progression.
Prolla, et al. Tumor Susceptibility and Spontaneous Mutation in Mice Deficient in Mlh-1, Pms-1 and Pms-2 DNA Mismatch Repair Nature Genetics 18: 276 (1998).
Baker et al. Involvement of Mouse Mlh-1 in DNA Mismatch Repair and Meiotic Crossing Over Nature Genetics 13: 336 (1996)
Mice with PMS2 gene deletion (-/-, +/-, +/+) are available for non-exclusive licensing.
For more information, contact:
Technology Development Manager