RGD Reference Report - PC12 cell model of inducible expression of mutant DISC1: new evidence for a dominant-negative mechanism of abnormal neuronal differentiation. - Rat Genome Database

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PC12 cell model of inducible expression of mutant DISC1: new evidence for a dominant-negative mechanism of abnormal neuronal differentiation.

Authors: Pletnikov, MV  Xu, Y  Ovanesov, MV  Kamiya, A  Sawa, A  Ross, CA 
Citation: Pletnikov MV, etal., Neurosci Res. 2007 Jul;58(3):234-44. Epub 2007 Mar 16.
RGD ID: 4107034
Pubmed: PMID:17418909   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neures.2007.03.003   (Journal Full-text)

A balanced chromosomal translocation, segregating with mental illnesses in a large Scottish family, interrupts the disrupted-in-schizophrenia 1 (DISC1) gene, which would result in loss of DISC1 function via haploinsufficiency or dominant-negative effects (or possibly could cause gain-of-function effects) if a truncated protein is present. To evaluate the effects of a predicted protein, mutant DISC1, we generated stable PC12 cell clones with inducible expression of mutant or full-length human DISC1 (hDISC1). Our study presents new observations that the inhibitory effects of mutant hDISC1 on NGF-induced neurite outgrowth are dependent on the level and timing of expression of mutant DISC1 and the concentrations of NGF, and are associated with altered sub-cellular distribution of endogenous DISC1 and ATF4, and decreased protein levels of LIS1. Thus, inducible expression of DISC1 in PC12 cell clones is a valuable in vitro model for further studying the molecular mechanisms likely due to loss of function of DISC1 relevant to the pathogenesis of major mental illnesses.

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
perinuclear region of cytoplasm  IDA 4107034 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Disc1  (DISC1 scaffold protein)

Objects referenced in this article
Gene Pafah1b1 platelet-activating factor acetylhydrolase 1b, regulatory subunit 1 Rattus norvegicus

Additional Information