Disc1 is mutated in the 129S6/SvEv strain and modulates working memory in mice.
Disrupted-In-Schizophrenia (DISC1) is a leading candidate schizophrenia susceptibility gene. Here, we describe a deletion variant in mDisc1 specific to the 129S6/SvEv strain that introduces a termination codon at exon 7, abolishes production of the full-length protein, and impairs working memory performance when transferred to the C57BL/6J genetic background. Our findings provide insights into how DISC1 variation contributes to schizophrenia susceptibility in humans and the behavioral divergence between 129S6/SvEv and C57BL/6J mouse strains and have implications for modeling psychiatric diseases in mice.
Human Neurogenetics Laboratory, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Hiroko
H
Koike
P Alexander
PA
Arguello
Mirna
M
Kvajo
Maria
M
Karayiorgou
Joseph A
JA
Gogos
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000473:pathology; D018388:Codon, Terminator; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D005091:Exons; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology*; D012559:Schizophrenia / Q000209:etiology / Q000235:genetics; D017384:Sequence Deletion; D013045:Species Specificity
D018388:Codon, Terminator; C412476:DISC1 protein, human; D018076:DNA, Complementary; C498794:Disc1 protein, mouse; D009419:Nerve Tissue Proteins