Key result
Overexpressing a 200-kb region of human chromosome 22q11.2 in mice drives hyperactivity and behavioral abnormalities.
Why the study?
The specific genes within human chromosome 22q11.2 that contribute to behavioral abnormalities including schizophrenia are poorly understood.
Does overexpression of a 200-kb region of human chromosome 22q11.2 cause behavioral abnormalities in mice?
Does overexpression of a 200-kb region of human chromosome 22q11.2 cause behavioral abnormalities in mice?
A specific 200-kb region of human chromosome 22q11.2 contains genes responsible for antipsychotic-responsive behavioral abnormalities in a mouse model, distinct from the physical defects mediated by Tbx1.
Narrows candidate genes for antipsychotic-responsive behaviors distinct from Tbx1; hypothesis-generating for human 22q11.2 neuropsychiatric risk.
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.
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Hiroi et al. (2005) studied Behavioral abnormalities (schizophrenia and other neuropsychiatric disorders). Overexpression of an approximately 200-kb region of human chromosome 22q11.2 vs. Tbx1 heterozygous mice / wild-type was evaluated on Behavioral abnormalities (hyperactivity, lack of habituation, impaired nesting behavior). Mice overexpressing a 200-kb region of human chromosome 22q11.2 exhibited spontaneous sensitization of hyperactivity, lack of habituation, and impaired nesting behavior.
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