title: Abnormal behavior in a chromosome-engineered mouse model for human 15q11-13 duplication seen in autism.
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.
authors: Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan.
authors: Jin
authors: J
authors: Nakatani
authors: Kota
authors: K
authors: Tamada
authors: Fumiyuki
authors: F
authors: Hatanaka
authors: Satoko
authors: S
authors: Ise
authors: Hisashi
authors: H
authors: Ohta
authors: Kiyoshi
authors: K
authors: Inoue
authors: Shozo
authors: S
authors: Tomonaga
authors: Yasuhito
authors: Y
authors: Watanabe
authors: Yeun Jun
authors: YJ
authors: Chung
authors: Ruby
authors: R
authors: Banerjee
authors: Kazuya
authors: K
authors: Iwamoto
authors: Tadafumi
authors: T
authors: Kato
authors: Makoto
authors: M
authors: Okazawa
authors: Kenta
authors: K
authors: Yamauchi
authors: Koichi
authors: K
authors: Tanda
authors: Keizo
authors: K
authors: Takao
authors: Tsuyoshi
authors: T
authors: Miyakawa
authors: Allan
authors: A
authors: Bradley
authors: Toru
authors: T
authors: Takumi
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000235:genetics* / Q000503:physiopathology*; D001522:Behavior, Animal; D002884:Chromosomes, Human, Pair 15; D033481:Chromosomes, Mammalian; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D007398:Interpersonal Relations; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism; D045442:Rotarod Performance Test; D015398:Signal Transduction
chemical_list: D044405:Receptor, Serotonin, 5-HT2C