A random mutagenesis screen to identify modifiers of epigenetic phenomena in the mouse.

Funding Activity

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Funded Activity Summary

In recent months, both the human and mouse genome projects have been completed. The main focus now for mammalian geneticists is to discover the function of the genes sequenced in these initiatives. One way to achieve this goal is by random mutagenesis followed by screening of mice for novel phenotypes. In the mouse, ethylnitosourea (ENU) is a chemical that can be used to perform the mutagenesis. ENU causes mutations in sperm. We are using ENU mutagenesis to search for genes that modify epigenetic states. Epigenetic modifications are alterations in the genome that do not change the DNA sequence, yet silence the expression of genes. Silencing occurs on a cell-by-cell basis within a tissue resulting in mosaic expression. Silencing can also occur between individuals of the same genetic makeup. For example, identical twins are occasionally found that have distinctly different characteristics, such as eye colour or severity of genetic disease. These differences may be the result of variable epigenetic modifications. However, very little is known about how these variable epigenetic modifications are controlled. We wish to find the proteins involved in establishing and maintaining epigenetic states. It is likely that these processes play a fundamental role in the determination of phenotype, both in normal development and disease.

Funded Activity Details

Start Date: 01-01-2004

End Date: 01-01-2008

Funding Scheme: NHMRC Project Grants

Funding Amount: $680,750.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Gene Expression

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

aging | cancer | cytosine methylation | early murine embryogenesis | epigenetic gene silencing | eukaryotic gene expression | fetal origins of adult disease | genetic disease | mutagenesis