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

Hiroi N,Zhu H,Lee M,Funke B,Arai M,Itokawa M,Kucherlapati R,Morrow B,Sawamura T,Agatsuma S

doi

10.1073/pnas.0509635102

keywords:

subject

Has Abstract

pub_date

2005-12-27 00:00:00

pages

19132-7

issue

52

eissn

0027-8424

issn

1091-6490

pii

0509635102

journal_volume

102

pub_type

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