Author/Authors :
Jin Nakatani، نويسنده , , Kota Tamada، نويسنده , , Fumiyuki Hatanaka، نويسنده , , Satoko Ise، نويسنده , , Hisashi Ohta، نويسنده , , Kiyoshi Inoue، نويسنده , , Shozo Tomonaga، نويسنده , , Yasuhito Watanabe، نويسنده , , Yeun Jun Chung، نويسنده , , Ruby Banerjee، نويسنده , , Kazuya Iwamoto، نويسنده , , Tadafumi Kato، نويسنده , , Makoto Okazawa، نويسنده , , Kenta Yamauchi، نويسنده , , Koichi Tanda، نويسنده , , Keizo Takao، نويسنده , , Tsuyoshi Miyakawa، نويسنده , , Allan Bradley، نويسنده , , Toru Takumi، نويسنده ,
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 Ca2+ 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.
