These Homer1 KO mice lack exon 2 of homer homolog 1 (Homer1) gene, abolishing gene expression. HOMER1 is a postsynaptic density scaffolding protein expressed in the central nervous system, as well as skeletal muscle, where it mediates the formation of large macromolecular complexes and regulates group 1 metabotrophic glutamate receptor function. Mice that are homozygous for this allele are viable and fertile. These mice exhibit myopathy characterized by decreased muscle fiber cross-sectional area and decreased skeletal muscle force generation. They display mild somatic growth retardation, poor motor coordination, enhanced sensory reactivity and learning deficits, and an increase in sensitivity to cocaine-induced locomotion and conditioned reward. They also display behavioral and neurochemical abnormalities consistent with the schizophrenia including decreased radial arm maze performance, impaired prepulse inhibition, enhanced behavioral despair, increased anxiety in a novel objects test, enhanced reactivity to novel environments, decreased instrumental responding for sucrose and enhanced methamphetamine-stimulated motor behavior.
