Abnormal behavior in a chromosome-engineered mouse model for human 15q11-13 duplication seen in autism.
Cell
; 137(7): 1235-46, 2009 Jun 26.
Article
em En
| MEDLINE
| ID: mdl-19563756
ABSTRACT
Substantial evidence suggests that chromosomal abnormalities contribute to the risk of autism. The duplication of human chromosome 15q11-13 is known to be the most frequent cytogenetic abnormality in autism. We have modeled this genetic change in mice by using chromosome engineering to generate a 6.3 Mb duplication of the conserved linkage group on mouse chromosome 7. Mice with a paternal duplication display poor social interaction, behavioral inflexibility, abnormal ultrasonic vocalizations, and correlates of anxiety. An increased MBII52 snoRNA within the duplicated region, affecting the serotonin 2c receptor (5-HT2cR), correlates with altered intracellular Ca(2+) responses elicited by a 5-HT2cR agonist in neurons of mice with a paternal duplication. This chromosome-engineered mouse model for autism seems to replicate various aspects of human autistic phenotypes and validates the relevance of the human chromosome abnormality. This model will facilitate forward genetics of developmental brain disorders and serve as an invaluable tool for therapeutic development.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transtorno Autístico
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Comportamento Animal
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Cromossomos Humanos Par 15
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Modelos Animais de Doenças
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Cell
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Japão