These targeted mice carry the tau mutation in floxed exon 4 of the mouse Csnk1e (casein kinase 1, epsilon; also called Ck1 epsilon) gene. Homozygotes show a shortened circadian period of behavior.
Dr. Joseph S. Takahashi, Univ Texas Southwestern Medical Ctr
The tau mutation of Syrian hamsters was the first mammalian circadian mutation discovered. These targeted mice carry the tau mutation in exon 4 of the mouse Csnk1e (casein kinase 1, epsilon; also called Ck1 epsilon) gene. Homozygotes show a shortened circadian period of behavior (in vivo) and suprachiasmatic nucleus firing rates (in vitro) due to accelerating Per1 (period homolog 1 (Drosophila))-dependent molecular feedback loops. LoxP sites located on either side of the mutant exon 4 enable tissue-specific cre excision of the catalytic domain to knock out expression. Homozygotes are viable and fertile with no overt deleterious phenotype.
A targeting vector was used to introduce the tau mutation (nucleotide C12555T; amino acid C178T) to exon 4, a loxP site to intron 3, and a NeoTK (neomycin/thymidine kinase) selection cassette flanked by loxP sites to intron 4. R1 embyronic stem (ES) cells derived from (129X1/SvJ x 129S1/Sv)F1- Kitl+ mice were used to create mutant animals. The floxed selection cassette was deleted from homologously recombined ES cell clones by transient transfection with a cre-expressing plasmid, leaving exon 4 flanked by loxP sites. The resulting mice were backcrossed to C57BL/6J for more than 8 generations by the donating laboratory.
|Allele Name||targeted mutation 1, Andrew S I Loudon|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Csnk1e, casein kinase 1, epsilon|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||A floxed neo cassette was inserted downstream of a modified exon 4 containing a C to T transition at base pair 12555 (C12555T) and an additional loxP site was inserted upstream of the modified exon 4. The neo cassette was removed by germ line, cre-mediated recombination that left the modified exon 4 floxed. The transition mimics a gain of function mutation identified in hamsters as having a destabilizing effect on Per1.|
|Mutations Made By|| |
Dr. Andrew Loudon, University of Manchester
When maintained as a live colony, heterozygotes or homozygotes may be bred.
When using the B6.129-Csnk1etm1Asil/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #016183 in your Materials and Methods section.
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