A Disc1 mutation differentially affects neurites and spines in hippocampal and cortical neurons.
Mol Cell Neurosci
; 54: 84-92, 2013 May.
Article
en En
| MEDLINE
| ID: mdl-23396153
A balanced chromosomal translocation segregating with schizophrenia and affective disorders in a large Scottish family disrupting DISC1 implicated this gene as a susceptibility gene for major mental illness. Here we study neurons derived from a genetically engineered mouse strain with a truncating lesion disrupting the endogenous Disc1 ortholog. We provide a detailed account of the consequences of this mutation on axonal and dendritic morphogenesis as well as dendritic spine development in cultured hippocampal and cortical neurons. We show that the mutation has distinct effects on these two types of neurons, supporting a cell-type specific role of Disc1 in establishing structural connections among neurons. Moreover, using a validated antibody we provide evidence indicating that Disc1 localizes primarily to Golgi apparatus-related vesicles. Our results support the notion that in vitro cultures derived from Disc1(Tm1Kara) mice provide a valuable model for future mechanistic analysis of the cellular and biochemical effects of this mutation, and can thus serve as a platform for drug discovery efforts.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Corteza Cerebral
/
Neuritas
/
Espinas Dendríticas
/
Hipocampo
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Mutación
/
Proteínas del Tejido Nervioso
Límite:
Animals
Idioma:
En
Revista:
Mol Cell Neurosci
Asunto de la revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos