Npas3 (neuronal PAS domain protein 3) encodes a transcription factor that localizes to the nucleus and may regulate genes involved in neurogenesis. Mutations in this gene are associated with schizophrenia and cognitive disability. Mice homozygous for this null allele exhibit a variety of behavioral phenotypes including: a 20% decrease in size, a shorter and irregular stride length, impaired social recognition, and increased locomotor activity. Neural precursor cell proliferation in the hippocampal dentate gyrus is decreased by 84% compared to wild-type mice resulting in a decrease in the thickness of the dentate gyrus granular cell layer. In addition, cortical interneuron density is reduced leading to a 21% reduction in cortical volume. Basal ganglia volumes also are decreased by 25%. Expression of reelin, a large extracellular matrix protein closely associated with schizophrenia, is substantially diminished in Npas3 null mice. Male homozygotes are infertile. Females are fertile, but fail to properly nest and mother their litters. This strain may be useful for studying schizophrenia.

Npas3 KO mice exhibit multiple behavioral phenotypes and altered brain morphologies including altered stride, increased locomotor activity, impaired social interaction, loss of neural precursor cells in the dentate gyrus and a reduction of cortical interneurons. This strain may be useful for studying schizophrenia.

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