|Functional Genomics Section
DOE Human Genome Program Contractor-Grantee Workshop
139. Gene Expression in Cardiac Hypertrophy as Measured by cDNA Microarrays
Carl Friddle, Teiichiro Koga, James
Bristow, and Edward M. Rubin
The mouse heart is an ideal model because it offers the benefits of a whole animal system in an organ comprised of relatively few cell types. We are studying the changes in heart gene expression that correspond to the onset and progression of cardiac hypertrophy. We wish to know the normal distribution of gene transcripts in the heart chambers in contrast to the distribution found in the hypertrophic state. Much has been learned about the expression profile of specific genes that play a role in cardiac hypertrophy (e.g.: ANF, MLC-2, c-Fos, c-Jun, Egr1). However, the discovery of new pathways involved in hypertrophy, and even the rapid identification of genes in known pathways, would benefit from an approach that analyzes thousands of genes in parallel. One could then perform a more detailed analysis of those genes that show a change in expression levels in conjunction with the onset of cardiac hypertrophy.
We have chosen to apply cDNA microarray technology to these questions. A array of over 3000 mouse EST clones was generated from the sequenced libraries of the IMAGE consortium. Included are ESTs from both heart, embryonic, liver and brain libraries. This array allows us to generate an expression profile for both the normal mouse heart and for hypertrophic tissues.
Hypertrophy was induced in vivo by treating mice with Isoproterenol. Heart weight was increased by 50% over the course of a week. Mice were sacrificed daily to generate a time course of hypertrophy induction. We then monitored the expression of the genes represented by our 3000 clones and used this information to identify classes of genes that are regulated in coordination with the onset and progression of cardiac hypertrophy.
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