Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse   Donating Investigator Dr. Joseph S. Takahashi,   Univ Texas Southwestern Medical Ctr

Description
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.

Development
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.

Related Strains

Strains carrying other alleles of Csnk1e

016184	B6.129(Cg)-Csnk1etm1.1Asil/J
010924	B6.129S4-Csnk1etm1.1Drw/J
010489	B6.129S4-Csnk1etm1Drw/J

View Strains carrying other alleles of Csnk1e     (3 strains)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Csnk1e^tm1Asil/Csnk1e⁺

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6

• behavior/neurological phenotype
• shortened circadian period
  • significant shortening of circadian period of behavior in vivo and suprachiasmatic nucleus firing rates in vitro in a gene dose-dependent manner   (MGI Ref ID J:135186)
  • heterozygous mice have 1.8 hr shorter circadian period than wild-type   (MGI Ref ID J:135186)
  • mutant mice are viable and fertile with no overt deleterious phenotype   (MGI Ref ID J:135186)

Csnk1e^tm1Asil/Csnk1e^tm1Asil

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6

• behavior/neurological phenotype
• shortened circadian period
  • significant shortening of circadian period of behavior in vivo and suprachiasmatic nucleus firing rates in vitro in a gene dose-dependent manner   (MGI Ref ID J:135186)
  • homozygous mice have 3.6 hr shorter circadian period than wild-type   (MGI Ref ID J:135186)
  • mutant mice are viable and fertile with no overt deleterious phenotype   (MGI Ref ID J:135186)

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Neurobiology Research
Circadian Rhythms
Cre-lox System
      loxP-flanked Sequences

Research Tools
Cre-lox System
      loxP-flanked Sequences

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Csnk1etm1Asil
Allele Name		targeted mutation 1, Andrew S I Loudon
Allele Type		Targeted (Floxed/Frt)
Common Name(s)		CK1epsilontau;
Mutation Made By		Dr. Andrew Loudon,   University of Manchester
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Csnk1e, casein kinase 1, epsilon
Chromosome		15
Gene Common Name(s)		AI426939; AI551861; AW457082; CK1epsilon; CKI epsilon; CKIepsilon; HCKIE; KC1epsilon; expressed sequence AI426939; expressed sequence AI551861; expressed sequence AW457082; tau;
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. [MGI Ref ID J:135186]

Genotyping

Genotyping Information

Genotyping Protocols

** Csnk1e*C178T, Pyrosequencing
Csnk1e^tm1Asil, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Meng QJ; Logunova L; Maywood ES; Gallego M; Lebiecki J; Brown TM; Sladek M; Semikhodskii AS; Glossop NR; Piggins HD; Chesham JE; Bechtold DA; Yoo SH; Takahashi JS; Virshup DM; Boot-Handford RP; Hastings MH; Loudon AS. 2008. Setting clock speed in mammals: the CK1 epsilon tau mutation in mice accelerates circadian pacemakers by selectively destabilizing PERIOD proteins. Neuron 58(1):78-88. [PubMed: 18400165]  [MGI Ref ID J:135186]

Additional References

Csnk1e^tm1Asil related

Maywood ES; Chesham JE; Meng QJ; Nolan PM; Loudon AS; Hastings MH. 2011. Tuning the Period of the Mammalian Circadian Clock: Additive and Independent Effects of CK1{varepsilon}Tau and Fbxl3Afh Mutations on Mouse Circadian Behavior and Molecular Pacemaking. J Neurosci 31(4):1539-44. [PubMed: 21273438]  [MGI Ref ID J:168543]

Maywood ES; Chesham JE; O'Brien JA; Hastings MH. 2011. A diversity of paracrine signals sustains molecular circadian cycling in suprachiasmatic nucleus circuits. Proc Natl Acad Sci U S A 108(34):14306-11. [PubMed: 21788520]  [MGI Ref ID J:175620]

Meng QJ; Maywood ES; Bechtold DA; Lu WQ; Li J; Gibbs JE; Dupre SM; Chesham JE; Rajamohan F; Knafels J; Sneed B; Zawadzke LE; Ohren JF; Walton KM; Wager TT; Hastings MH; Loudon AS. 2010. Entrainment of disrupted circadian behavior through inhibition of casein kinase 1 (CK1) enzymes. Proc Natl Acad Sci U S A 107(34):15240-5. [PubMed: 20696890]  [MGI Ref ID J:163807]

Mohawk JA; Baer ML; Menaker M. 2009. The methamphetamine-sensitive circadian oscillator does not employ canonical clock genes. Proc Natl Acad Sci U S A 106(9):3519-24. [PubMed: 19204282]  [MGI Ref ID J:146448]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Breeding & Husbandry	When maintained as a live colony, heterozygotes or homozygotes may be bred.

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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