PARENT SESSION

(M364) MUTANT MOUSE MODELS OF INFERTILITY: A RESOURCE FOR NEW REPRODUCTIVE GENE DISCOVERIES.

Pendola, Janice¹, Sweeney, Sheila ¹, Lothrop, Heather¹, Lessard, Carl¹, Schimenti, John², Handel, Mary Ann¹, Eppig, John¹, ¹ The Jackson Laboratory, Bar Harbor, ME² Cornell University, Ithaca, NY

ABSTRACT- The ReproGenomics program at The Jackson Laboratory utilizes ENU mutagenesis and phenotype screening to generate mutant mouse models of infertility for the scientific community. In the past 2.5 years, 36 infertile mutant mouse lines with recessive mutations leading to complete infertility scored in natural matings have been identified for phenotype analysis and gene mapping. The phenotypes assessed in these mutant lines include hormone production, gonad histology, gametogenesis, fertilization and pre-implantation development. Thus far, 28 infertility mutations have been mapped to distinct chromosomal regions. Taken together, these mouse models display a wide range of reproductive phenotypes including meiotic arrest, sperm morphology and motility defects, absence of growing oocytes and follicles, poor pre-implantation development and unexplained infertility. Interestingly, 20 of the 28 mapped mutations affect only males, and the majority of these mutations result in abnormal sperm morphology and motility. This observation suggests that spermatogenesis, and especially spermiogenesis, is more genetically complex or involves less genetic redundancy than oogenesis. These valuable and unique reproductive mutant mouse resources are available through our program web site at http://reprogenomics.jax.org. Ultimately, dissection of gene function from these mutant phenotypes will deepen our understanding of known pathways, and identify new reproductive pathways, as well as lead to therapies for infertile couples and reveal novel human contraceptive targets. (Supported by NIH-HD PO1 HD42137 to JJE, MAH, JCS)

KEY WORDS: gametogenesis, infertility, mutagenesis, genomics