Provisional mapping of quantitative trait loci modulating the acoustic startle response and prepulse inhibition of acoustic startle.
Prepulse inhibition (PPI) of the acoustic startle response (ASR) is a form of sensorimotor gating, defined as an inhibition of the startle response when a low intensity stimulus, the prepulse, precedes the startling stimulus. Deficits in PPI have been reported in schizophrenia and other psychiatric/neurological disorders, and correlate with symptom severity in schizophrenia, suggesting that deficient PPI per se or abnormalities in neural circuits regulating PPI may cause some symptoms of schizophrenia. If so, then genes conferring reduced PPI may contribute toward genetic vulnerability to schizophrenia. Studies with selectively bred rodent strains indicate that PPI is under genetic control; however, the identity of the relevant genes is unknown. The current study used recombinant congenic mouse strains derived from C57BL/6J and A/J parents to assess genetic variability in PPI and in ASR and to identify provisional quantitative trait loci (QTLs) modulating these phenotypes. Significant between-strain differences in ASR and in PPI at each of several prepulse intensities (75, 80, 85, 90, 95 dB) were found. Correlations between PPI at the various prepulse intensities were highly significant, suggesting appreciable overlap in genetic regulation of PPI across prepulse intensities. Five QTLs (chromosomes 3, 5, 7, 16) associated with PPI across all prepulse intensities, but not with ASR, were identified. Two additional QTLs (chromosomes 2, 11) associated with both PPI and ASR were found. Fifteen QTLs were associated with ASR alone. Data on genotypes of informative congenic strains were used to support probable involvement of loci modulating PPI and to narrow the probable chromosomal location of QTLs. If confirmed, these QTLs may suggest candidate genes directing novel mechanisms for regulation of PPI
Joober
Ridha
R
Department of Psychiatry and of Neurology and Neurosurgery, Montreal, Quebec, Canada.
Zarate
Jean Mary
JM
Rouleau
Guy André
GA
Skamene
Emil
E
Boksa
Patricia
P
D000161:Acoustic Stimulation / Q000379:methods; D000818:Animals; D002874:Chromosome Mapping / Q000379:methods*; D005819:Genetic Markers / Q000235:genetics; D007266:Inhibition, Psychological; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D040641:Quantitative Trait Loci / Q000235:genetics*; D013216:Reflex, Startle / Q000235:genetics*; D013045:Species Specificity
D005819:Genetic Markers