Genomic survey of prepulse inhibition in mouse chromosome substitution strains

M. P. Leussis, M. L. Frayne, M. Saito, E. M. Berry, K. A. Aldinger, G. N. Rockwell, Ronald P Hammer, A. E. Baskin-Hill, J. B. Singer, J. H. Nadeau, P. Sklar, T. L. Petryshen

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Prepulse inhibition (PPI) is a measure of sensorimotor gating, a pre-attentional inhibitory brain mechanism that filters extraneous stimuli. Prepulse inhibition is correlated with measures of cognition and executive functioning, and is considered an endophenotype of schizophrenia and other psychiatric illnesses in which patients show PPI impairments. As a first step toward identifying genes that regulate PPI, we performed a quantitative trait locus (QTL) screen of PPI phenotypes in a panel of mouse chromosome substitution strains (CSSs). We identified five CSSs with altered PPI compared with the host C57BL/6J strain: CSS-4 exhibited decreased PPI, whereas CSS-10, -11, -16 and -Y exhibited higher PPI compared with C57BL/6J. These data indicate that A/J chromosomes 4, 10, 11, 16 and Y harbor at least one QTL region that modulates PPI in these CSSs. Quantitative trait loci for the acoustic startle response were identified on seven chromosomes. Like PPI, habituation of the startle response is also disrupted in schizophrenia, and in the present study CSS-7 and -8 exhibited deficits in startle habituation. Linkage analysis of an F 2 intercross identified a highly significant QTL for PPI on chromosome 11 between positions 101.5 and 114.4 Mb (peak LOD = 4.54). Future studies will map the specific genes contributing to these QTLs using congenic strains and other genomic approaches. Identification of genes that modulate PPI will provide insight into the neural mechanisms underlying sensorimotor gating, as well as the psychopathology of disorders characterized by gating deficits.

Original languageEnglish (US)
Pages (from-to)806-816
Number of pages11
JournalGenes, Brain and Behavior
Volume8
Issue number8
DOIs
StatePublished - Nov 2009

Fingerprint

Chromosomes
Quantitative Trait Loci
Startle Reflex
Sensory Gating
Surveys and Questionnaires
Prepulse Inhibition
Schizophrenia
Genes
Endophenotypes
Chromosomes, Human, Pair 10
Chromosomes, Human, Pair 11
Chromosomes, Human, Pair 4
Psychopathology
Acoustics
Cognition
Psychiatry
Phenotype
Brain

Keywords

  • Behavior
  • Cognition
  • Linkage
  • Mouse genetics
  • Psychiatric disorders
  • Psychopathology
  • Quantitative trait locus
  • Sensorimotor gating
  • Startle

ASJC Scopus subject areas

  • Behavioral Neuroscience
  • Genetics
  • Neurology

Cite this

Leussis, M. P., Frayne, M. L., Saito, M., Berry, E. M., Aldinger, K. A., Rockwell, G. N., ... Petryshen, T. L. (2009). Genomic survey of prepulse inhibition in mouse chromosome substitution strains. Genes, Brain and Behavior, 8(8), 806-816. https://doi.org/10.1111/j.1601-183X.2009.00526.x

Genomic survey of prepulse inhibition in mouse chromosome substitution strains. / Leussis, M. P.; Frayne, M. L.; Saito, M.; Berry, E. M.; Aldinger, K. A.; Rockwell, G. N.; Hammer, Ronald P; Baskin-Hill, A. E.; Singer, J. B.; Nadeau, J. H.; Sklar, P.; Petryshen, T. L.

In: Genes, Brain and Behavior, Vol. 8, No. 8, 11.2009, p. 806-816.

Research output: Contribution to journalArticle

Leussis, MP, Frayne, ML, Saito, M, Berry, EM, Aldinger, KA, Rockwell, GN, Hammer, RP, Baskin-Hill, AE, Singer, JB, Nadeau, JH, Sklar, P & Petryshen, TL 2009, 'Genomic survey of prepulse inhibition in mouse chromosome substitution strains', Genes, Brain and Behavior, vol. 8, no. 8, pp. 806-816. https://doi.org/10.1111/j.1601-183X.2009.00526.x
Leussis MP, Frayne ML, Saito M, Berry EM, Aldinger KA, Rockwell GN et al. Genomic survey of prepulse inhibition in mouse chromosome substitution strains. Genes, Brain and Behavior. 2009 Nov;8(8):806-816. https://doi.org/10.1111/j.1601-183X.2009.00526.x
Leussis, M. P. ; Frayne, M. L. ; Saito, M. ; Berry, E. M. ; Aldinger, K. A. ; Rockwell, G. N. ; Hammer, Ronald P ; Baskin-Hill, A. E. ; Singer, J. B. ; Nadeau, J. H. ; Sklar, P. ; Petryshen, T. L. / Genomic survey of prepulse inhibition in mouse chromosome substitution strains. In: Genes, Brain and Behavior. 2009 ; Vol. 8, No. 8. pp. 806-816.
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