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Northwestern on trail of gene mutations that trigger sex reversal

Northwestern University has received a five-year, $2.8 million grant from the National Institutes of Health (NIH) to identify the gene mutations that cause sex reversal, a condition in which individuals have the chromosomes of one sex but the physical attributes of the other, resulting in XY females or XX males.

Heading the gene study at the Feinberg School of Medicine at Northwestern University are J. Larry Jameson, M.D., Irving S. Cutter Professor and chair of medicine, and Jeffrey Weiss, research associate professor of medicine.

The study is one of four collaborative projects funded by the National Institute of Child Health and Human Development to identify mutations in mice that cause developmental and fertility defects and to characterize the mutations responsible for these defects. The research projects are part of the NIH's initiative to determine the function of mammalian genes.

To identify mutations in the sex determination genes that cause sex reversal, Jameson and Weiss will employ a technique known as genome-wide mutagenesis. The process uses a chemical called ENU (N-ethyl-N-nitrosourea) to create a broad spectrum of point mutations throughout the mouse genome that are passed on to subsequent generations. The various mutations introduced by ENU mutagenesis are then studied and, once there is evidence of a single gene mutation for a given trait, the researchers can pinpoint the gene using positional cloning.

The Northwestern investigators will screen tens of thousands of mice harboring random, chemically induced mutations for sex reversal, characterize the mutations in detail and, it is hoped, find the responsible genes. This will involve comparing phenotypic (appearance) sex to genotypic sex (presence or absence of the male-determining factor Sry) in the genome.

The mice progeny from the sex determination/sex reversal study will be made available to the scientific community for future research. Weiss b
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Contact: Elizabeth Crown
e-crown@northwestern.edu
312-503-8928
Northwestern University
15-Jan-2003


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