Chen C, Rainnie DG, Greene RW, Tonegawa S:
Abnormal fear response and aggressive behavior in mutant mice
deficient for alpha-calcium-calmodulin kinase II.
Science 1994 Oct 14;266(5183):291-4
ABSTRACT
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.
