DYRK1A-haploinsufficiency in mice causes autistic-like features and febrile seizures.
Neurobiol Dis
; 110: 180-191, 2018 02.
Article
em En
| MEDLINE
| ID: mdl-29223763
ABSTRACT
Mutations and copy number variants affecting DYRK1A gene encoding the dual-specificity tyrosine phosphorylation-regulated kinase 1A are among the most frequent genetic causes of neurodevelopmental disorders including autism spectrum disorder (ASD) associated with microcephaly, febrile seizures and severe speech acquisition delay. Here we developed a mouse model harboring a frame-shift mutation in Dyrk1a resulting in a protein truncation and elimination of its kinase activity site. Dyrk1a+/- mice showed significant impairments in cognition and cognitive flexibility, communicative ultrasonic vocalizations, and social contacts. Susceptibility to hyperthermia-induced seizures was also significantly increased in these mice. The truncation leading to haploinsufficiency of DYRK1A in mice thus recapitulates the syndromic phenotypes observed in human patients and constitutes a useful model for further investigations of the mechanisms leading to ASD, speech delay and febrile seizures.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Tirosina Quinases
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Proteínas Serina-Treonina Quinases
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Convulsões Febris
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Modelos Animais de Doenças
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Transtorno do Espectro Autista
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Neurobiol Dis
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Japão