These Camk2a knock-out mice exhibit deficiency in long-term hippocampal potentiation with impairment in spatial learning.
Alcino J. Silva, University of California, Los Angeles
Mice homozygous for the Camk2atm1Sva targeted mutation are viable but are reported not to breed. Homozygous mutant mice show no obvious anatomical defects in the nervous system. Postsynaptic mechanisms are intact, but long-term hippocampal potentiation (LTP), an electrophysiological manifestation of increased synapse strength, is deficient. These mutant mice show specific impairment in spatial learning, indicating that LTP is important to spatial though not necessarily to non-spatial memory. In a more recent study heterozygotes displayed normal offensive aggression. Heterozygotes exhibit a decreased fear response and an increase in defensive aggression. Homozygotes (in which both copies of the gene are absent) exhibit more pronounced behavior suggesting a gene dosage effect.
This targeted mutant was made in the Laboratory of Dr. Susumu Tonegawa at the Massachusetts Institute of Technology. A replacement-type targeting vector was used which resulted in the deletion of the entire inhibitory domain and five amino acids in the amino end of the calmodulin-binding domain. Targeting was done in E14 ES cells.
|Allele Name||targeted mutation 1, Alcino Silva|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Camk2atm1; alpha-CaMKII-; alphaCaMKII-; alphaCaMKIInull|
|Gene Symbol and Name||Camk2a, calcium/calmodulin-dependent protein kinase II alpha|
|Gene Synonym(s)||CAMKA; MRD53; PK2CDD; PKCCD; R74975; alpha-CaMKII; expressed sequence R74975; mKIAA0968|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||A 130 bp DNA segment encoding the inhibitory domain and five amino acids of the calmodulin-binding domain was replaced with a neomycin selection cassette. Northern blot analysis on brain RNA derived from homozygous mice confirmed that no detectable transcript is produced from this allele. Western blot analysis on forebrain samples from homozygous mice demonstrated that no detectable protein is expressed from this allele.|
|Mutations Made By|| |
Alcino Silva, University of California, Los Angeles
We maintaining a live colony C57BL/6J females (Stock No. 000664) may be bred to heterozygous male. The donating investigator reports that carriers of both sexes will cannibalize the pups. Male needs to be removed as soon as it is obvious that the female is pregnant.
When using the α-CaMKII KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #002362 in your Materials and Methods section.
|Heterozygous Males or Wild-type females for Camk2a<tm1Sva> ONLY|
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