behavior/neurological
• at ~3 months of age, both male and female homozygotes show a significant reduction in the total time spent in the novel arm of the Y-maze recognition task relative to wild-type controls
• both male and female mutants spent an equal time exploring all three arms of the Y-maze, suggesting a failure to recognize the novel arm
• gonadectomy reduces Y-maze responses in male and female wild-type controls, but has no effect in mutant mice
• after gonadectomy, there is no significant difference in the percentage time spent in the novel arm between mutant mice and wild-type controls
• notably, male and female mutants are NOT found to display increased anxiety-induced freezing or reduced explorative behavior in the elevated plus maze task
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• at 6 months of age, male (but not female) homozygotes develop compulsive behaviors including excessive barbering, grooming and wheel running
• male-specific excessive wheel running and grooming activities are accompanied by a significant decrease in catechol-O-methyltransferase (COMT1) protein expression in the hypothalamus and can be reversed by 3 weeks of 17beta-estradiol treatment
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• at 6 months of age, male homozygotes display extreme barbering with a significant increase in facial hair loss relative to wild-type controls
• no significant differences are observed in barbering activity between female homozygotes and wild-type control females
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• at 6 months of age, male homozygotes show a significant increase in grooming activity, both in terms of frequency of initiation and duration of grooming, as analyzed during a 20-min period immediately after a water-mist spray
• male-specific excessive grooming activities are accompanied by a significant decrease in COMT1 protein expression in the hypothalamus and can be reversed by 3 weeks of 17beta-estradiol treatment
• no significant differences in grooming activity are observed between female homozygotes and wild-type control females
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• at 6 months of age, male homozygotes display a significant increase in wheel running activity relative to wild-type controls; excessive wheel running is male-specific and can be suppressed upon 17beta-stradiol replacement
• in contrast, male homozygotes display a significantly reduced general ambulatory activity, indicating a specific increase in wheel running as opposed to a general hyperactivity
• no significant differences are observed in either wheel running or ambulatory activity between female homozygotes and wild-type control females
• no stereotypic behaviors such as barmouthing, jumping, somersaulting or route-tracing are observed in male homozygotes housed in an "enriched environment"
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