Chromosome 22 Implicated in Abnormal Behavior in Mice
Region previously linked to schizophrenia and behavioral disorders in humans
FRIDAY, Dec. 23 (HealthDay News) -- A region of human chromosome 22 previously associated with schizophrenia and other neuropsychiatric disorders can cause behavioral abnormalities when it is overexpressed in mice, according to a study published online Dec. 19 in the Proceedings of the National Academy of Sciences Early Edition.
Noboru Hiroi, Ph.D., of the Albert Einstein College of Medicine, Bronx, New York, and colleagues genetically engineered mice to overexpress either one to two copies, or eight to 10 copies of a 200-kb region of human chromosome 22. The researchers also generated mice heterozygous for Tbx1 (T-box 1, a transcription factor), one of the four genes in this region. Mice were tested at five weeks of age or at two to four months.
The transgenic mice showed defects in nesting behavior, and both sets of mice displayed a sensitized hyperactivity and lack of habituation, which could be reversed by treatment with antipsychotic drugs. Although Tbx1 heterozygosity had previously been associated with physical abnormalities in mice, the Tbx1 heterozygous mice did not display any behavioral abnormalities, the researchers found.
"Our data suggest that this 200-kb region of 22q11.2 contains one or more genes that are responsible for some behavioral disorders associated with 22q11.2 duplications, and that heterozygosity of Tbx1 alone is not responsible for all behavioral abnormalities in 22q11.2 deletion cases," Hiroi and colleagues conclude.