These mice carry a targeted knockout of the Prkcz (protein kinase C, zeta) gene, disrupting expression of both PKM-ζ and PKC-ζ proteins. Homozygotes demonstrate reduced anxiety behavior and increased ethanol consumption in intermittent consumption procedures.
Robert O. Messing, The University of Texas at Austin
PKM-ζ is a constitutively active form of atypical protein kinase C that is transcribed from the Prkcz (protein kinase C, zeta) gene. It is expressed exclusively in the brain and implicated in the maintenance of long-term memory. PKC-ζ, also expressed from the Prkcz gene, is primarily expressed outside of the central nervous system.
Animals homozygous for this knockout allele lack expression of both PKC-ζ and PKM-ζ proteins encoded by the Prkcz gene, as determined by western blot. They show normal baseline behavior, motor function, and sensory perception, but display reduced anxiety-like behavior. In light-dark box tests, homozygous null male mice spend 51% more time and travel 36% farther in the lit compartment than male wild-type mice. On the elevated plus maze, homozygous null mice of both genders make more entries into the open arms and tend to spend more time there than wild-type mice. Homozygous null male mice consume more ethanol than wild-type mice after repeated periods of intermittent ethanol exposure. Mice do not show deficits in learning or memory in tests of cued fear conditioning, novel object recognition, object location recognition, conditioned place preference for cocaine or ethanol, or motor learning, when compared with wild-type littermates.
Exon 9 of the targeted gene, encoding the purine binding site in the catalytic domain of PKC-ζ and PKM-ζ proteins, was flanked by loxP sites and this mutation was introduced by homologous recombination into 129S6/SvEvTac-derived W4 embryonic stem (ES) cells. Resultant mice were crossed with a C57BL/6J background Flp strain to excise an Frt-flanked neomycin selection cassette, then crossed with C57BL/6J background CMV-cre mice to excise exon 9. This strain was backcrossed to C57BL/6J for 11 generations by the donating laboratory.
|Allele Name||targeted mutation 1.1, Robert O Messing|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Prkcz, protein kinase C, zeta|
|Strain of Origin||129S6/SvEvTac|
|Molecular Note||Exon 9 was floxed and removed by cre-mediated recombination. Western blot analysis confirmed the absence of protein expression in the brain and kidney.|
Heterozygotes are viable and fertile.
When using the B6.129S6(Cg)-Prkcztm1.1Msg/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #022998 in your Materials and Methods section.
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