403. Mouse genetic models for sensorimotor gating deficits

Abstract

Several patient populations with neuropsychiatric disorders, including schizophrenia, have impaired sensorimotor gating as measured using the prepulse inhibition (PPI) paradigm. Several studies using various mouse genetic models to understand the genetic basis for PPI will be discussed. Evaluating the PPI response in different inbred strains of mice we found that PPI is a polygenic trait. The chromosomal regions influencing PPI in a segregating F2 mice have initially been mapped using QTL strategies. The PPI response appears to have a relatively high heritable rate, but only a few suggestive QTL loci (LOD score 2 to 2.5) have been identified. Different gene-targeted mutant mice have also been a valuable tool for studying the role of single gene mutations in PPI. Although many mutant mice appear to have normal PPI, we have identified the Dv11-deficient mouse as a potential animal model system for studying schizophrenia-related traits in mice. However, in contrast to what might have been predicted, mice deficient in the α7 nicotinic receptor subunit displayed normal sensorimotor gating. Most recently we found an abnormal PPI response in mice with a deletion of chromosome 16 in a region syntenic for DiGeorge syndrome. Mice with a deletion of chromosome 16 showed significantly greater levels of PPI compared to their wild-type controls, which is opposite of what we might have predicted since patients with DiGeorge syndrome often display “schizophrenic-like” behaviors. We believe that using various types of mouse genetic models systems will help to better understand the biological basis for sensorimotor gating deficits associated with neuropsychiatric disorders.