TY - JOUR
T1 - A Review of Disrupted-in-Schizophrenia-1 (disc1)
T2 - Neurodevelopment, Cognition, and Mental Conditions
AU - Ishizuka, Koko
AU - Paek, Matt
AU - Kamiyaand, Atsushi
AU - Sawa, Akira
PY - 2006/6/15
Y1 - 2006/6/15
N2 - Disrupted-In-Schizophrenia-1 (DISC1) is a promising candidate gene for schizophrenia (SZ) and bipolar disorder (BP), but its basic biology remains to be elucidated. Accumulating genetic evidence supports that DISC1 is associated with some aspects of cognitive functions relevant to SZ and BP. Here, we provide a summary of the current updates in biological studies of DISC1. Disrupted-In-Schizophrenia-1, preferentially expressed in the forebrain, has multiple isoforms with potential posttranslational modifications. Disrupted-In-Schizophrenia-1 protein occurs in multiple subcellular compartments, which include the centrosome, microtubule fractions, postsynaptic densities, actin cytoskeletal fractions, the mitochondria, and the nucleus. Recent studies have clarified that DISC1 mediates at least centrosome-dynein cascade and cyclic adenosine monophosphate (cAMP) signaling. Furthermore, both cytogenetic and cell biological studies consistently suggest that an overall loss of DISC1 function (either haploinsufficiency or dominant-negative, or both) may be associated with SZ and BP. On the basis of these findings, production of DISC1 genetically engineered mice is proposed as a promising animal model for SZ and BP. Several groups are currently generating DISC1 mice and starting to characterize them. In this review, the advantages and disadvantages of each animal model are discussed.
AB - Disrupted-In-Schizophrenia-1 (DISC1) is a promising candidate gene for schizophrenia (SZ) and bipolar disorder (BP), but its basic biology remains to be elucidated. Accumulating genetic evidence supports that DISC1 is associated with some aspects of cognitive functions relevant to SZ and BP. Here, we provide a summary of the current updates in biological studies of DISC1. Disrupted-In-Schizophrenia-1, preferentially expressed in the forebrain, has multiple isoforms with potential posttranslational modifications. Disrupted-In-Schizophrenia-1 protein occurs in multiple subcellular compartments, which include the centrosome, microtubule fractions, postsynaptic densities, actin cytoskeletal fractions, the mitochondria, and the nucleus. Recent studies have clarified that DISC1 mediates at least centrosome-dynein cascade and cyclic adenosine monophosphate (cAMP) signaling. Furthermore, both cytogenetic and cell biological studies consistently suggest that an overall loss of DISC1 function (either haploinsufficiency or dominant-negative, or both) may be associated with SZ and BP. On the basis of these findings, production of DISC1 genetically engineered mice is proposed as a promising animal model for SZ and BP. Several groups are currently generating DISC1 mice and starting to characterize them. In this review, the advantages and disadvantages of each animal model are discussed.
KW - DISC1
KW - knockout mice
KW - neurodevelopment
KW - schizophrenia
KW - transgenic mice
UR - http://www.scopus.com/inward/record.url?scp=33745221854&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33745221854&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2006.03.065
DO - 10.1016/j.biopsych.2006.03.065
M3 - Review article
C2 - 16797264
AN - SCOPUS:33745221854
VL - 59
SP - 1189
EP - 1197
JO - Biological Psychiatry
JF - Biological Psychiatry
SN - 0006-3223
IS - 12
ER -