Identify Sex Determination Genes by ENU Mutagenesis

Project: Research project

Project Details

Description

DESCRIPTION (provided by applicant): Sex determination in mammals is governed by a series of genetic switches that influence cell fate and differentiation during critical periods of development. Remarkably, the primordial fetal gonad is bipotential and the precursor gonadal cells can develop along either a male (testis) or female (ovary) pathway, depending on which genes are expressed. The main goal of this project is to identify key genes that regulate gonadal development and phenotypic sex. To this end, the investigators propose to screen mice for sex-reversal, manifest as XY phenotypic females or as XX phenotypic males, taking advantage of the existing Northwestern University Genome Wide ENU Mutagenesis Center. The specific aims of this project are: Aim 1: To screen progeny of ENU-mutagenized mice for sex reversal. Mice will be characterized genetically for the presence or absence of the Y-chromosomal Sry gone. At age 21 days, they will be classified as phenotypically male or female. This screen will include at least 10,000 mice per year. Aim 2: To characterize the gonadal phenotype of mice with sex-reversal. Morphologic, hormonal, histologic, and developmental analyses will be used to characterize the gonadal (testis and ovary) defects associated with sexreversal. Functional analyses will assess spermatogenesis in males or ovulation in females. These initial studies will be followed by more detailed characterizations of altered gene and protein expression using in situ hybridization, quantitative RT-PCR, immunohistology, and western blot studies. Microarray analyses will be used to identify altered genetic pathways, particularly during key stages of gonadal development. Aim 3: To perpetuate germline transmission of mutations associated with sex-reversal and gonadal dysgenesis and to map the genetic locus of the defect. Aim 4: To act as a national resource for mouse mutants by providing access to phenotypic screening analyses "online". In addition to listing iden
StatusFinished
Effective start/end date9/27/026/30/07

Funding

  • National Institute of Child Health and Human Development (5 U01 HD043425-05)

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