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Publication : Fine mapping of QTL for prepulse inhibition in LG/J and SM/J mice using F(2) and advanced intercross lines.

First Author  Samocha KE Year  2010
Journal  Genes Brain Behav Volume  9
Issue  7 Pages  759-67
PubMed ID  20597988 Mgi Jnum  J:178214
Mgi Id  MGI:5297684 Doi  10.1111/j.1601-183X.2010.00613.x
Citation  Samocha KE, et al. (2010) Fine mapping of QTL for prepulse inhibition in LG/J and SM/J mice using F(2) and advanced intercross lines. Genes Brain Behav 9(7):759-67
abstractText  Prepulse inhibition (PPI) of the startle response is a measure of sensorimotor gating, a process that filters out extraneous sensory, motor and cognitive information. Humans with neurological and psychiatric disorders, including schizophrenia, obsessive-compulsive disorder and Huntington's disease, exhibit a reduction in PPI. Habituation of the startle response is also disrupted in schizophrenic patients. In order to elucidate the genes involved in sensorimotor gating, we phenotyped 472 mice from an F(2) cross between LG/J x SM/J for PPI and genotyped these mice genome-wide using 162 single nucleotide polymorphism (SNP) markers. We used prepulse intensity levels that were 3, 6 and 12 dB above background (PPI3, PPI6 and PPI12, respectively). We identified a significant quantitative trait locus (QTL) on chromosome 12 for all three prepulse intensities as well as a significant QTL for both PPI6 and PPI12 on chromosome 11. We identified QTLs on chromosomes 7 and 17 for the startle response when sex was included as an interactive covariate and found a QTL for habituation of the startle response on chromosome 4. We also phenotyped 135 mice from an F(34) advanced intercross line (AIL) between LG/J x SM/J for PPI and genotyped them at more than 3000 SNP markers. Inclusions of data from the AIL mice reduced the size of several of these QTLs to less than 5 cM. These results will be useful for identifying genes that influence sensorimotor gaiting and show the power of AIL for fine mapping of QTLs.
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