Dysbindin-1 reductions appear to be common in dysfunctional brain areas of schizophrenia cases. In the absence of a dysbindin-1 knockout, sandy (sdy) mice provide our only means of studying the potential contribution of this protein to clinical features of schizophrenia in live animals. Our knowledge of sandy mice is reviewed here. These mice have a deletion mutation that arose spontaneously in DBA/2J mice in the gene encoding dysbindin-1 (Dtnbp1). This null protein mutation (Dtnbp1(sdy)) leads to an absence of dysbindin-1 in homozygotes, as well as reductions in several direct and indirect binding partners of dysbindin-1 that contribute to the protein assembly known as BLOC-1. Studies of sdy mice on the original DBA/2J background and on a C57BL/6J background indicate that the Dtnbp1(sdy) mutation does not affect viability, basic sensory or motor functions, or measures of anxiety and motivation. Such studies do indicate, however, that the mutation affects several biological functions, including adrenal neurosecretion and pre- and postsynaptic aspects of dopaminergic, glutamatergic, and GABAergic transmission. These effects and those on prepulse inhibition, social interaction, and diverse aspects of spatial memory suggest that homozygous sdy mice may model various features of schizophrenia.
2009 Elsevier B.V. All rights reserved.