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Science 14 October 1994:
Vol. 266. no. 5183, pp. 291 - 294
DOI: 10.1126/science.7939668
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Articles

Science, Vol 266, Issue 5183, 291-294
Copyright © 1994 by American Association for the Advancement of Science

articles

Abnormal fear response and aggressive behavior in mutant mice deficient for alpha-calcium-calmodulin kinase II

C Chen, DG Rainnie, RW Greene, and S Tonegawa

Howard Hughes Medical Institute, Center for Cancer Research, Cambridge, MA.

Mice deficient for the gene encoding alpha-calcium-calmodulin-dependent kinase II (alpha-CaMKII knockout mice) provide a promising tool to link behavioral and cellular abnormalities with a specific molecular lesion. The heterozygous mouse exhibited a well-circumscribed syndrome of behavioral abnormalities, consisting primarily of a decreased fear response and an increase in defensive aggression, in the absence of any measured cognitive deficits. Unlike the heterozygote, the homozygote displayed abnormal behavior in all paradigms tested. At the cellular level, both extracellular and whole-cell patch clamp recordings indicated that serotonin release in putative serotonergic neurons of the dorsal raphe was reduced. Thus, alpha-CaMKII knockout mice, in particular the heterozygote, may provide a model for studying the molecular and cellular basis underlying emotional disorders involving fear and aggression.


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