title: Abnormal behavior in mice mutant for the Disc1 binding partner, Dixdc1.
abstract: Disrupted-in-Schizophrenia-1 (DISC1) is a genetic susceptibility locus for major mental illness, including schizophrenia and depression. The Disc1 protein was recently shown to interact with the Wnt signaling protein, DIX domain containing 1 (Dixdc1). Both proteins participate in neural progenitor proliferation dependent on Wnt signaling, and in neural migration independently of Wnt signaling. Interestingly, their effect on neural progenitor proliferation is additive. By analogy to Disc1, mutations in Dixdc1 may lead to abnormal behavior in mice, and to schizophrenia or depression in humans. To explore this hypothesis further, we generated mice mutant at the Dixdc1 locus and analyzed their behavior. Dixdc1(-/-) mice had normal prepulse inhibition, but displayed decreased spontaneous locomotor activity, abnormal behavior in the elevated plus maze and deficits in startle reactivity. Our results suggest that Dixdc1(-/-) mice will be a useful tool to elucidate molecular pathophysiology involving Disc1 in major mental illnesses.
authors: Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94158, USA.
authors: S
authors: S
authors: Kivimäe
authors: P-M
authors: PM
authors: Martin
authors: D
authors: D
authors: Kapfhamer
authors: Y
authors: Y
authors: Ruan
authors: U
authors: U
authors: Heberlein
authors: J L R
authors: JL
authors: Rubenstein
authors: B N R
authors: BN
authors: Cheyette
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D004843:Epistasis, Genetic / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*
chemical_list: C513335:DIXDC1 protein, human; C498794:Disc1 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins