International Mammalian Genome Society

The 16th International Mouse Genome Conference (2002)

Plenary Presentations * Oral Presentations *
Poster Presentations: Complex Genetics and Disease Modifiers * Developmental Genetics * Functional Genomics * Gene Discovery * Genetic Manipulations to Alter Gene Function * Mouse Models: Human Disease and Pharmacogenetics * Sequence Annotation and Comparative Analysis of Genomes *
Attendees * Sponsors * Table of Contents * Photographs * Awards

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Oral Presentation

Monday 18 November

17:45 - 18:00 HRS

AN ENU MUTAGENESIS SCREEN TO IDENTIFY VARIANTS THAT AFFECT GENE EXPRESSION FROM THE INACTIVE X CHROMOSOME

LH Chadwick
Case Western Reserve University

Co-Authors: Willard HF
Institutions: University Hospitals of Cleveland

In order to equalize X linked gene expression between male and female mammals, one X chromosome is stably silenced in each female somatic cell. While X inactivation is one of the most striking examples of epigenetic regulation, relatively little is known about the specific trans-acting factors that are involved in this process. We are using two complementary approaches to identify such factors and their effects on inactive X chromatin. First, we are examining expression of X-linked genes (Utx, Smcx, and Eif2s3x) that are known to escape inactivation in mice. Smcx expression from the inactive X (Xi) was previously shown to be approximately half the active X expression. Using an allele-specific RT-PCR assay, we characterized the expression of Utx and found only a 20% reduction in expression from the Xi. This difference suggests that local chromatin environment may influence the degree of Xi expression. Our second approach is to use these assays as a sensitive marker of inactive X chromatin in an ENU mutagenesis screen to identify dominant mutations that affect levels of Xi expression.  This screen is complementary to a previous screen that identified autosomal dominant mutations involved in the initial stage of X inactivation (Percec et al., Science 296:1136. 2002). To date, we have analyzed 67 G1 females at Utx and 44 G1 females at Smcx. Eight females displayed significant (>2 SD) differences in Xi expression of one of these genes, relative to an unmutagenized control population. These animals are being progeny tested to determine heritibility of this trait.