Role of Oocyte Loss in Ovarian Surface Mesothelial Cell Transformation
Abstract
Three Specific Aims (SA) were proposed to test in mice the hypothesis that accelerated oocyte loss caused by Bclw deficiency or Bax gain-of-function drives ovarian surface mesothelial cell (OSMC) transformation: 1) characterize preneoplastic changes in OSMC of between mice with increasing age; 2) determine if disruption of the gene encoding Bax, a Bclw interacting partner required for oocyte apoptosis, rescues the compromised oocyte survival and the OSMC transformation phenotype observed in aging bclw mice; and 3) test if targeting overexpression of bax to only growing oocytes accelerates oocyte depletion and causes OSMC transformation To date we have generated the mice needed to complete SA 1 and 2, and have confirmed the occurrence of OSMC transformation in 9+ month bclw mutants (SA 1) However, there is no evidence of progression to invasive carcinoma by 20+ months of age (SA 1) We have confirmed that simultaneous inactivation of bax restores the compromised oocyte endowment in bclw mutants to normal (SA 2) Finally, we have constructed the zp3-bax minigene and have begun to generate transgenic mice expressing Bax only in growing oocytes (SA 3) 1 and have shown in another mouse model that accelerated oocyte loss is directly involved in ovarian tumorigenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2002
- Accession Number
- ADA413259
Entities
People
- Grant R. Macgregor
- Jonathan L. Tilly
Organizations
- Massachusetts General Hospital