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Mouse Mlh-1 (-/-) Embryonic Cell Line

 

OHSU # 0416

Technology Overview

Mutations in the DNA mismatch repair pathway have been shown to be involved in the development of certain cancers, most notably those of the colon and endometrium. MLH1 is one of the genes involved in DNA repair during cell division. MLH1 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.

Market Summary

·         MLH1 deficiency results in increased spontaneous mutations throughout the genome.

·         Of the ~6000 people in the US who develop HNPCC (hereditary non-polyposis

colorectal cancer) each year, ~30% have a germline mutation in MLH1.

·         Women who are MLH1- have an 80% chance of developing endometrial cancer.

·         MLH1 protein is part of a repair complex that includes PMS2, among other proteins.

·         In humans, most germline mutation carriers are heterozygotes (+/-) carrying recessive

MLH1 mutations in all tissues. When the other MLH1 gene is inactivated in a particular

cell, in the lining of the colon for example, the mutation rate in that cell and its progenitors

increases dramatically, mutations accumulate and tumors can arise.

Knockout Phenotype

·         MLH1 mice are prone to cancer (>80% of the mice have tumors after 1 year as

compared with control mice where <5% have tumors): intestinal adenomas and

adenocarcinomas, lymphomas and skin cancers.

·         MLH1 cells are more resistant to alkylating agents.

Applications

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.

2.       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 Mlh1 mutation carriers

(+/-). Also, provide a system to test new and existing drugs for their ability to slow diet provoked progression.

Publications

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)

Licensing Opportunity

Mouse embryonic fibroblasts with MLH1 null mutation (-/-, +/-, +/+) are available for non-exclusive licensing.

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For more information, contact:

Dennis Hanson
Technology Development Manager
503-494-5861