Fine mapping of QTL for prepulse inhibition in LG/J and SM/J mice using F-2 and advanced intercross lines

K. E Samocha; J. E Lim; R Cheng; G Sokoloff; A. A Palmer

doi:10.1111/j.1601-183X.2010.00613.x

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Fine mapping of QTL for prepulse inhibition in LG/J and SM/J mice using F-2 and advanced intercross lines

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Fine mapping of QTL for prepulse inhibition in LG/J and SM/J mice using F-2 and advanced intercross lines

K. E Samocha, J. E Lim, R Cheng, G Sokoloff and A. A Palmer

Genes, brain and behavior, Vol.9(7), pp.759-767

10/01/2010

DOI: 10.1111/j.1601-183X.2010.00613.x

PMCID: PMC3749925

PMID: 20597988

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Abstract

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.

Behavioral Sciences

Life Sciences & Biomedicine

Neurosciences

Neurosciences & Neurology

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Details

Title: Subtitle: Fine mapping of QTL for prepulse inhibition in LG/J and SM/J mice using F-2 and advanced intercross lines
Creators: K. E Samocha - University of Chicago
J. E Lim - Duke University
R Cheng - University of Chicago
G Sokoloff - University of Chicago
A. A Palmer - University of Chicago
Resource Type: Journal article
Publication Details: Genes, brain and behavior, Vol.9(7), pp.759-767
Publisher: WILEY
DOI: 10.1111/j.1601-183X.2010.00613.x
PMID: 20597988
PMCID: PMC3749925
ISSN: 1601-1848
eISSN: 1601-183X
Number of pages: 9
Language: English
Date published: 10/01/2010
Academic Unit: Psychological and Brain Sciences
Record Identifier: 9984256837602771

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