Mice that are heterozygous for the Csnk1a casein kinase 1, delta targeted mutation, when kept in constant darkness for 10 days, exhibit a longer free-running period than wild-type controls. This mutant mouse strain may be useful in studies of circadian rhythm and behavior.
David R. Weaver, Univ of Massachusetts Medical School
Mice that are heterozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical abnormalities. Homozygotes die during late gestation and perinatally, with no homozygotes at weaning age. Homozygous embryos are smaller (approximately 30% less than control weight) than wild-type controls at embryonic day 18-19. A truncated non-functional gene product (protein), lacking residues 26 to 62, is detected by Western blot analysis and cotransfection assays of homozygotes. The truncated protein does not phosphorylate or degrade PER1, period homolog 1 (Drosophila), and PER2, period homolog 2 (Drosophila), proteins. After being kept in constant darkness for 10 days, heterozygotes exhibit a longer free-running period than wild-type controls.
A loxP site flanked targeting vector containing neomycin resistance and thymidine kinase genes was utilized in the construction of this mutant. This selection cassette was inserted downstream of exon 2 of the targeted gene, and another loxP site was inserted upstream of exon 2. This construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice, and then crossed to mice expressing Cre recombinase in the testis (Protamine-cre, on the C57BL6J background). Mice that no longer contained exon 2 or the Cre recombinase transgene were backcrossed to C57BL/6J for 10 generations. Upon arrival at The Jackson Laboratory, the mice were crossed with C57BL/6J once to establish the colony.
|Allele Name||targeted mutation 1.1, David R Weaver|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Csnk1d, casein kinase 1, delta|
|Strain of Origin||129S4/SvJae|
|Molecular Note||Germ line, cre mediated recombination removed exon 2. The absence of exon 2 leads to the deletion of residues 26 and 62 and produces a non-functional truncated protein.|
|Mutations Made By|| |
David Weaver, Univ of Massachusetts Medical School
When maintaining a live colony, these mice can be bred as heterozygotes. Homozygotes die during late gestation and perinatally, with no homozygotes at weaning age.
When using the B6.129S4-Csnk1dtm1.1Drw/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #010923 in your Materials and Methods section.