Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA or protein) is detected by RT-PCR or Western blot analysis. Synaptic plasticity, as assayed by long-term potentiation (LTP) and long-term depression (LTD), in mutant mice is deficient. Homozygotes exhibit diminished contextual and auditory fear memory. Cyclic AMP-responsive element binding protein (CREB) activation by fear conditioning is absent in the amygdala and decreased in the hippocampus. Thymocyte maturation is impaired. Both CD4+ and CD8+, single positive, thymocyte levels are reduced. This mutant mouse strain may be useful in studies examining learning and memory or related to thymocyte development.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 3 and adjacent introns. The construct was electroporated into 129X1/SvJ-derived RW4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were crossed to C57BL/6 mice, and then backcrossed to the same for 15 generations.
|Allele Name||targeted mutation 1, Talal A Chatila|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Camk4-; CaMKIV/Gr KO|
|Gene Symbol and Name||Camk4, calcium/calmodulin-dependent protein kinase IV|
|Strain of Origin||129X1/SvJ|
|Molecular Note||The replacement of the third exon, which encodes the ATP binding site in the catalytic domain of the kinase, with a neomycin resistance gene rendered the enzyme catalytically inactive and prone to degradation.|
|Mutations Made By|| |
Talal Chatila, Boston Children's Hospital
When maintaining a live colony, these mice can be bred as homozygotes.
When using the CaMKIV/Gr KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004994 in your Materials and Methods section.