Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Biol Psychiatry ; 78(7): 485-95, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-25802080

RESUMO

BACKGROUND: Quantitative genetic analysis of basic mouse behaviors is a powerful tool to identify novel genetic phenotypes contributing to neurobehavioral disorders. Here, we analyzed genetic contributions to single-trial, long-term social and nonsocial recognition and subsequently studied the functional impact of an identified candidate gene on behavioral development. METHODS: Genetic mapping of single-trial social recognition was performed in chromosome substitution strains, a sophisticated tool for detecting quantitative trait loci (QTL) of complex traits. Follow-up occurred by generating and testing knockout (KO) mice of a selected QTL candidate gene. Functional characterization of these mice was performed through behavioral and neurological assessments across developmental stages and analyses of gene expression and brain morphology. RESULTS: Chromosome substitution strain 14 mapping studies revealed an overlapping QTL related to long-term social and object recognition harboring Pcdh9, a cell-adhesion gene previously associated with autism spectrum disorder. Specific long-term social and object recognition deficits were confirmed in homozygous (KO) Pcdh9-deficient mice, while heterozygous mice only showed long-term social recognition impairment. The recognition deficits in KO mice were not associated with alterations in perception, multi-trial discrimination learning, sociability, behavioral flexibility, or fear memory. Rather, KO mice showed additional impairments in sensorimotor development reflected by early touch-evoked biting, rotarod performance, and sensory gating deficits. This profile emerged with structural changes in deep layers of sensory cortices, where Pcdh9 is selectively expressed. CONCLUSIONS: This behavior-to-gene study implicates Pcdh9 in cognitive functions required for long-term social and nonsocial recognition. This role is supported by the involvement of Pcdh9 in sensory cortex development and sensorimotor phenotypes.


Assuntos
Atividade Motora/fisiologia , Reconhecimento Psicológico/fisiologia , Córtex Sensório-Motor/patologia , Filtro Sensorial/fisiologia , Percepção Social , Animais , Aprendizagem por Associação/fisiologia , Mapeamento Cromossômico , Cognição/fisiologia , Dendritos/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Atividade Motora/genética , Fenótipo , Locos de Características Quantitativas , Córtex Sensório-Motor/crescimento & desenvolvimento , Córtex Sensório-Motor/fisiopatologia , Filtro Sensorial/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...