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.
journal_name
Proc Natl Acad Sci U S Aauthors
Hiroi N,Zhu H,Lee M,Funke B,Arai M,Itokawa M,Kucherlapati R,Morrow B,Sawamura T,Agatsuma Sdoi
10.1073/pnas.0509635102keywords:
subject
Has Abstractpub_date
2005-12-27 00:00:00pages
19132-7issue
52eissn
0027-8424issn
1091-6490pii
0509635102journal_volume
102pub_type
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