Mouse Model of Chromosome 15q13.3 Microdeletion Syndrome Demonstrates Features Related to Autism Spectrum Disorder.
J Neurosci
; 35(49): 16282-94, 2015 Dec 09.
Article
em En
| MEDLINE
| ID: mdl-26658876
ABSTRACT
The chromosome 15q13.3 microdeletion is a pathogenic copy number variation conferring epilepsy, intellectual disability, schizophrenia, and autism spectrum disorder (ASD). We generated mice carrying a deletion of 1.2 Mb homologous to the 15q13.3 microdeletion in human patients. Here, we report that mice with a heterozygous deletion on a C57BL/6 background (D/+ mice) demonstrated phenotypes including enlarged/heavier brains (macrocephaly) with enlarged lateral ventricles, decreased social interactions, increased repetitive grooming behavior, reduced ultrasonic vocalizations, decreased auditory-evoked gamma band EEG, and reduced event-related potentials. D/+ mice had normal body weight, activity levels, sensory gating, and cognitive abilities and no signs of epilepsy/seizures. Our results demonstrate that D/+ mice represent ASD-related phenotypes associated with 15q13.3 microdeletion syndrome. Further investigations using this chromosome-engineered mouse model may uncover the common mechanism(s) underlying ASD and other neurodevelopmental/psychiatric disorders representing the 15q13.3 microdeletion syndrome, including epilepsy, intellectual disability, and schizophrenia. SIGNIFICANCE STATEMENT Recently discovered pathologic copy number variations (CNVs) from patients with neurodevelopmental/psychiatric disorders show very strong penetrance and thus are excellent candidates for mouse models of disease that can mirror the human genetic conditions with high fidelity. A 15q13.3 microdeletion in humans results in a range of neurodevelopmental/psychiatric disorders, including epilepsy, intellectual disability, schizophrenia, and autism spectrum disorder (ASD). The disorders conferred by a 15q13.3 microdeletion also have overlapping genetic architectures and comorbidity in other patient populations such as those with epilepsy and schizophrenia/psychosis, as well as schizophrenia and ASD. We generated mice carrying a deletion of 1.2 Mb homologous to the 15q13.3 microdeletion in human patients, which allowed us to investigate the potential causes of neurodevelopmental/psychiatric disorders associated with the CNV.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Convulsões
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Encéfalo
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Transtornos Cromossômicos
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Transtorno do Espectro Autista
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Deficiência Intelectual
Tipo de estudo:
Etiology_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
J Neurosci
Ano de publicação:
2015
Tipo de documento:
Article