This small research project focuses on the role of kinesin 8, Kif18A, which has an essential function in cell division and is broadly expressed, yet is uniquely required in the developing germ line. Mutations in mammalian Kif18A lead to germ cell depletion and ultimately infertility;however, infertility in mutant mice is not fully penetrat and is dependent on strain background. Therefore, there are genetic factors that ameliorate infertility in the context of Kif18A ablation. The unique role of Kif18a in germ line development has only recently been revealed and a mechanism for Kif18a function in the germ line has not been established. The overall goal of this small research project is to provide the basic biological data required to establish the mechanism by which Kif18A functions in germ line development and to create a genetic dataset for the discovery of the molecular pathways that modulate Kif18A dependent germ cell depletion. These data will contribute to the foundation of a larger research program focused on the specialization of germ cell division in the mammalian germ line, where maintenance of genome integrity is integral to gametogenesis and, critically, fertility.

Public Health Relevance

Germ cell depletion is a leading cause of infertility among men and women, with a significant economic impact, as evidenced by the nearly 3 billion dollars spent world- wide on assisted reproductive technologies. In the United States, nearly 12% of couples are infertile. Germ cell insufficiency leading to azoospermia, oligospermia, anovulation or oligoovulation is caused by a variety of factors that are either genetic or are heavily influenced by the genetics of the individual. Data generated by this project will contribute to our understanding of how genes that are critical for genome integrity are uniquely required in the germ line, and importantly will provide a foundational dataset that will lead to the identificationof pathways that allow for restoration of fertility in the context of mutations that would otherwise cause infertility.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Small Research Grants (R03)
Project #
1R03HD078485-01A1
Application #
8769699
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Taymans, Susan
Project Start
2014-09-17
Project End
2016-08-31
Budget Start
2014-09-17
Budget End
2015-08-31
Support Year
1
Fiscal Year
2014
Total Cost
$87,500
Indirect Cost
$37,500
Name
Jackson Laboratory
Department
Type
DUNS #
042140483
City
Bar Harbor
State
ME
Country
United States
Zip Code
04609