A 200-kb region of human chromosome 22q11.2 confers antipsychotic-responsive behavioral abnormalities in mice.
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.
Hiroi
Noboru
N
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
Zhu
Hongwen
H
Lee
Moonsook
M
Funke
Birgit
B
Arai
Makoto
M
Itokawa
Masanari
M
Kucherlapati
Raju
R
Morrow
Bernice
B
Sawamura
Takehito
T
Agatsuma
Soh
S
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
D000662:Amphetamines; D014150:Antipsychotic Agents; D003024:Clozapine