title: A 200-kb region of human chromosome 22q11.2 confers antipsychotic-responsive behavioral abnormalities in mice.
abstract: Human chromosome 22q11.2 has been implicated in various behavioral abnormalities, including schizophrenia and other neuropsychiatric/behavioral disorders. However, the specific genes within 22q11.2 that contribute to these disorders are still poorly understood. Here, we show that an approximately 200-kb segment of human 22q11.2 causes specific behavioral abnormalities in mice. Mice that overexpress an approximately 200-kb region of human 22q11.2, containing CDCrel, GP1Bbeta, TBX1, and WDR14, exhibited spontaneous sensitization of hyperactivity and a lack of habituation. These effects were ameliorated by antipsychotic drugs. The transgenic mice were also impaired in nesting behavior. Although Tbx1 has been shown to be responsible for many physical defects associated with 22q11.2 haploinsufficiency, Tbx1 heterozygous mice did not display these behavioral abnormalities. Our results show that the approximately 200-kb region of 22q11.2 contains a gene(s) responsible for behavioral abnormalities and suggest that distinct genetic components within 22q11.2 mediate physical and behavioral abnormalities.
authors.affiliation: Laboratory of Molecular Psychobiology, Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. hiroi@aecom.yu.edu
authors.forename: Noboru
authors.initials: N
authors.lastname: Hiroi
authors.forename: Hongwen
authors.initials: H
authors.lastname: Zhu
authors.forename: Moonsook
authors.initials: M
authors.lastname: Lee
authors.forename: Birgit
authors.initials: B
authors.lastname: Funke
authors.forename: Makoto
authors.initials: M
authors.lastname: Arai
authors.forename: Masanari
authors.initials: M
authors.lastname: Itokawa
authors.forename: Raju
authors.initials: R
authors.lastname: Kucherlapati
authors.forename: Bernice
authors.initials: B
authors.lastname: Morrow
authors.forename: Takehito
authors.initials: T
authors.lastname: Sawamura
authors.forename: Soh
authors.initials: S
authors.lastname: Agatsuma
mesh_terms: D000015:Abnormalities, Multiple; D000662:Amphetamines / Q000378:metabolism; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000648:ultrastructure*; D003024:Clozapine / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011618:Psychotic Disorders / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics; D013997:Time Factors
chemical_list: D000662:Amphetamines; D014150:Antipsychotic Agents; D003024:Clozapine