The overall objective of this project is to build a detailed characterization of the oocyte/follicle phenotype of selected mutations discovered by the Core screen using a phenotype-driven mutagenesis paradigm. This is an essential step in a functional genomic approach to resolve mechanisms of oocyte/follicle development. The Core screen will identify infertile females, many with failed ovarian follicle development, ovulation, or oocytes defection in growth, progression of meiosis, fertilization, or competence to undergo pre-implantation development. The focus of this project will be to characterize the phenotypes of these infertile females with emphasis on those exhibiting failure of oogenesis and folliculogenesis. The phenotypes will be posted on our Program Project Website and will be distributed to investigators requesting them.
Aim 1 will be to select and characterize mutants whose phenotypes suggest abnormalities in these processes. These analysis will be comprised of both well-established methods for analysis (ovarian transplantation, microscopy, expression of known marker genes, as well as innovative methods developed in this laboratory (reaggregated chimeric ovaries and in-vitro development and function). In addition to the morphological and functional studies described in Aim 1, comprehensive phenotyping depends upon the establishment of new molecular markers of the development of oocytes and their companion somatic cells.
In Aim 2 A, novel markers expressed during normal oocyte and granulosa cell development that will be useful to further characterize the consequences of mutations will be identified.
In Aim 2 B, these marker genes will be used to characterized the consequences of mutations on the patterns of gene expression. Thus, the phenotype characterizations will include morphological, functional, and molecular components. These characterizations will enable members of the community of Reproductive and Developmental biologists to select mutations for further studies that will make a major contribution to understanding the etiology of infertility in women.
Showing the most recent 10 out of 32 publications
