International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 181 - MICROARRAY GENE EXPRESSION PROFILING IN CONGENIC STRAINS TO IDENTIFY CANDIDATE GENES FOR A QUANTITATIVE BEHAVIORAL TRAIT

Rodriguez de Ledesma A M
The Genomics Institute, Wadsworth Center-NYState Dept. of Health

Co-Authors: Bolivar V J, Isabelle J, Symula D, Flaherty L
Institutions: The Genomics Institute, Wadsworth Center-NYState Dept. of Health

We are using knockout/congenic mouse strains as a system for isolating and mapping quantitative trait loci. Because most of knockout strains are bred to B6 for a number of generations, we developed a breeding scheme to distinguish the effects of 129 flanking sequences from the targeted ablation. To evaluate our scheme, we screened several knockout/congenic strains in a battery of behavioral tests and found that the B6.129-IL10-/- congenic strain behaves differently from C57BL/6J (B6) in our open field test. Using newly developed subcongenic strains, made in our laboratory, we determined that the gene(s) influencing this open field trait, maps to a 50 Mb 129-derived region proximal to the IL10 gene on chromosome 1 and clearly distinguishable from IL10. Microarray analysis (Affymetrix 430A and B chips) was undertaken to identify genes that are expressed differently between the subcongenic and its inbred partner. Specific regions of the brain were examined including the amygdala and hippocampus, known to influence performance on the open field test. In amygdala, we found 120 genes differentially expressed. Of these, 9 named or annotated and 5 RIKEN transcripts mapped to the 129-flanking interval. The rest map to other chromosomes or regions outside this 50 Mb region. Two genes are strong candidates for influencing open field activity based on their known cellular function and are being validated by quantitative RT-PCR. These data will provide suitable candidate genes for further studies as well as demonstrate the degree of differential gene expression that occurs between congenic strains and their inbred partners.


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