International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


ORAL PRESENTATION

MONDAY 10 NOVEMBER
10:15 – 10:30 HRS

FUNCTIONAL ANNOTATION OF MUTANT MOUSE ES CELL LINES BY EXPRESSION PROFILING

Symula D J
Wadsworth Center

Co-Authors: Curley B
Institutions: Wadsworth Center

A high-throughput, in vitro phenotype screen would allow powerful forward genetic approaches to be applied to mouse embryonic stem (ES) cell mutagenesis experiments. We have assessed the ability of expression profiling to detect the effects of heterozygous mutations in ES cells and to specifically and accurately categorize mutants. Heterozygous mutation in either of two well characterized genes, the cell cycle regulator, cyclin D kinase 4 (Cdk4) or cholesterol transport regulator, ATP binding cassette transporter family A, member 1 (Abca1), resulted in expression profile changes highly specific to each mutant line. Few genes associated with pluripotency were differentially expressed between either mutant and its parental cell line. Rather, the functions of many of the affected genes were consistent with the reported functions of the mutant gene in each ES cell line. The heterozygous Cdk4 mutation affected expression of many genes involved in cell growth and proliferation, while the heterozygous Abca1 mutation altered genes associated with lipid homeostasis, the cytoskeleton, and vesicle trafficking. Livers of mice heterozygous for the same Abca1 mutation showed alterations in many of the same processes, as defined by Gene Ontology categories, while acting on different genes. These results indicate that mutant ES cell expression profiles may reflect the impact of a heterozygous mutation in multiple cell types, identifying mutants of interest and guiding subsequent in vivo experiments.


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