International Mammalian Genome Society

The 13th International Mouse Genome Conference
October 31-November 3, 1999

Table of Contents * Structure * Bioinformatics * Sequence * Mapping * New Tools * Gene Discovery * Developmental * Mutagenesis * Functional Genomics

H9 Mutagenesis Screens for Mouse Gametogenesis Mutants

Brian Libby1, Robert Munroe1, Rebecca Bergstrom1, Andreas Lengeling2, Maja Bucan2,3, and John Schimenti1. 1The Jackson Laboratory, Bar Harbor, ME 04609; 2Center for Neurobiology and Behavior, Department of Psychiatry, and 3Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104

Genes essential to mammalian fertility are likely to be great in number, but remain largely unknown as infertile animals are often unnoticed, or are not pursued, in global mutagenesis screens.  To detect such genes, we are generating a large mutant screening population using two distinct mutant generation strategies.  One approach examines the entire mouse genome by treating ES cells with ethyl methanesulfonate (EMS), a potent point mutagen of flies and nematodes, followed by generating families of mice for screening.  Thus far, at least two independent sterility mutant lineages have been established.  Homozygous males belonging to one mutant line (which we have tentatively dubbed Mei1) lack mature spermatozoa, and germ cells are arrested at meiosis I prophase.  The fertility of Mei1 females is being investigated.

        Two other mutants exhibit round sperm heads, and testes with regions of agametic seminiferous tubules.  Recently, mapping studies of Mei1 and this second mutation have commenced.

        A second approach has been designed to eliminate the need for linkage mapping as it focuses on a subset of the genome, namely the Rump white (Rw) interval of proximal Chr 5.  Mice bearing large chromosomal deficiencies within Rw have been generated using traditional ES cell technologies from radiation-treated cells.  We have mice that collectively have deletions spanning half of the Rw region.  Efforts to remove the remaining portions are underway.   These mice are being used in complementation crosses with spouses containing ethylnitrosourea (ENU)-treated genomes.  Mutations detected using this strategy will be further delimited using deletions with nested breakpoints prior to gene cloning using standard molecular strategies.



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