# GENETIC STUDIES OF GONADAL SEX DETERMINATION IN MAMMALS

> **NIH NIH R01** · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · 1994 · $279,743

## Abstract

In mammals, gonadal sex determination is the process that determines
whether the embryonic gonad will develop as testis or as ovary.  The
long-term objective of this project is a detailed understanding of the
genes involved in this binary switching system.  The guiding premise of
this project is that an abundance of mutations, occurring naturally in
both humans and mice, provide powerful points of entry for
investigating,the sex-determining mechanism.  Such defects in
sex-determining genes result, in both humans and in mice, in abnormal
sexual differentiation and infertility.

A chief goal of the present application is identification, via genetic
linkage analysis in mice, of two or more autosomal genes that play
critical roles in gonadal sex determination, and analysis of the
structure and function of those genes in both mice and humans.  Should
this line of inquiry lead to the cloning of putative sex-determining
genes, the functions of those genes will be tested in transgenic mice.
These studies may result in highly defined mouse models of abnormal
sexual development.

A related goal of the present application is the characterization of
human mutations that result in sex reversal.  Among the humans mutations
to be characterized by detailed studies at the DNA level are: 1) gross
structural anomalies of the Y chromosome associated with sex reversal of
XX or XY individuals, 2) Y-chromosomal point mutations resulting in
ovarian development in XY individuals, and 3) autosomal or X-linked
mutations resulting in sex reversal of XX or XY individuals.

A third goal of the present application is identification of the
biological functions of the mammalian ZFY and ZFX genes, which encode
zinc-finger proteins, via manipulations of the genes in cultured cells
and in transgenic mice.

## Key facts

- **NIH application ID:** 2198556
- **Project number:** 5R01HD022532-08
- **Recipient organization:** WHITEHEAD INSTITUTE FOR BIOMEDICAL RES
- **SAM.gov UEI:** C186U32QSBR9
- **Principal Investigator:** David C. Page
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $279,743
- **Award type:** 5
- **Project period:** 1986-12-01 → 1997-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2198556

## Citation

> US National Institutes of Health, RePORTER application 2198556, GENETIC STUDIES OF GONADAL SEX DETERMINATION IN MAMMALS (5R01HD022532-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2198556. Licensed CC0.

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