Suggestive evidence for a quantitative trait locus on chromosome 3 for prepulse inhibition in the mouse

Objective: Schizophrenic patients display diminished prepulse inhibition (PPI) of the acoustic startle response. Thus, PPI in rodents may be used as an animal model for a neurophysiological trait in schizophrenia amenable to quantitative trait loci (QTL) mapping. Method: From an F2 intercross generation of C57BL/ 6J mice (diminished PPI) with AKR/J mice (normal PPI), we have genotyped 96 mice with extreme PPI using 121 markers covering the mouse genome at least every 20 cM. Mapmaker/QTL was used to search for areas of mouse chromosomes exhibiting a higher correlation of marker similarity to PPI score than expected by chance. Results: Heritability for PPI is estimated to be 0.64 +/- 0.06 from the phenotyping data. The most interesting linkage results from the preliminary scan of the extreme PPI mice reveal a region near marker D3Mit25 showing a suggestive linkage (MLOD = 2.5; P <0.0024) under recessive inheritance. Conclusions: There is reasonable preliminary evidence that PPI is transmitted via detectable QTLs from the initial measures in this F2 intercross design (C57BL/ 6JxAKR/J). We detected suggestive evidence for linkage of proximal chromosome 3 to PPI in the mouse, and are currently genotyping all 600 mice from the F2 intercross at the five most significant regions from the genomic scan of the extreme PPI mice, which we estimate will increase the available information by another 40-50%.