Male mice homozygous for a null mutation in the DNA mismatch repair gene, Pms2, are sterile and produce only abnormal spermatozoa. Previous analysis of spermatocyte nuclei from these mice demonstrated abnormalities in the initiation of synapsis between homologous chromosomes during meiotic prophase I. These results implicate a unique function for Pms2 and DNA mismatch repair processes in meiotic recombination. Several questions arise from these initial studies of Pms2 deficient mice. How is Pms2 protein associated with the spermatocyte chromosomes? What is the nature of the protein complex within which Pms2 functions during meiosis? Are these previously identified or unique proteins? How does this complex function in meiotic recombination? To analyze the role of Pms2 protein in meiosis, Pms2 antisera will be used to detect the sites of Pms2 action during prophase I of meiosis. Proteins that specifically interact with Pms2 during meiosis will be identified. Using the yeast two hybrid system a mouse testis cDNA expression library will be screened using a Pms2 fusion protein. The proteins that show specific interaction will be tested for in vitro association with Pms2. Pms2 interacting proteins will be used also to generate antisera. The antisera will be localized in meiotic nuclei and the staining pattern compared to that of Pms2.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM057525-02
Application #
2910417
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1998-05-01
Project End
2003-04-30
Budget Start
1999-05-01
Budget End
2000-04-30
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of California Berkeley
Department
Nutrition
Type
Schools of Earth Sciences/Natur
DUNS #
094878337
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Gurtu, Vanessa E; Verma, Shelly; Grossmann, Allie H et al. (2002) Maternal effect for DNA mismatch repair in the mouse. Genetics 160:271-7