Mouse Genome Informatics
involves: 129S/SvEv * 129S1/Sv * 129X1/SvJ * C57BL/6J
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
• mutants exhibit random vectors through the open field unlike wild-type mice that primarily run around the outside chamber and spend most of the time in the corners, indicating abnormal anxiety levels
• mutants are more likely to venture into the center of the field during the first few minutes of the test session, indicating decreased thigmotaxis
• in the elevated plus maze, mutants spend less time in the closed arm and more time in the open arm compared to wild-type mice, indicating decreased anxiety levels
• mutants exhibit reduced freezing in response to a conditioning tone previously associated with a mild footshock, however the freezing response is intact as behavioral responses to a fear-associated context are normal
• activity during conditioning tone presentation is normal, however activity is elevated during tone presentation in the retrieval test
• although mutants are able to learn forced alteration rule in the automated eight-arm radial maze, mutants show a time-dependent decrease in nonmatching performance, indicating spatial working memory deficits
• mutants respond more strongly to the 120 dB stimulus then wild-type mice
• mutants show enhanced startle responses at the highest amplitudes (loudest pulses)
• mutants exhibit elevated horizontal activity compared to wild-type littermates and this behavior is nonhabituating over repeated trials
• juvenile, newly weaned mutants also exhibit increased horizontal activity
• antipsychotic drug clozapine ameliorates the persistent hyperactivity
• the NMDAR antagonist, MK-801, has a reduced effect on hyperactivity in mutants compared to wild-type mice
• mutants show an increase in stereotypies in the open field test compared to wild-type littermates, most pronounced at the beginning of a 2 hour test session
• mutants show increased stereotypic behavior in 30 minute open field trials over 5 consecutive days, indicating behavior is nonhabituating
• mutants are unable to distinguish between familiar and novel conspecifics compared to wild-type mice which spend more time with the novel conspecifics
• in a test for social isolation, mutants spend more time in the center compartment (a space that is separated from the other mice) than in ends of chamber where novel conspecifics were placed, indicating a preference for social isolation

nervous system

Mouse Models of Human Disease
Schizophrenia; SCZD 181500 J:194146