These transgenic mice express a T44A mutant form of the human CSNK1D (casein kinase 1, delta) gene that has been associated with symptoms of Familial Advanced Sleep Phase Syndrome (FASPS) and migraine.
Ying-Hui Fu, University of California, San Francisco
Louis Ptacek, University of California, San Francisco
Mutations in the human CSNK1D (casein kinase 1, delta) gene have been associated with symptoms of Familial Advanced Sleep Phase Syndrome (FASPS) and migraines. A T44A (threonine to alanine) amino acid mutation disrupts a phosphorylation site, shifts circadian patterns in subjects manifesting as symptoms of early sleep times and early-morning awakening, and predisposes them to migraine.
Hemizygous transgenic mice express 2-3 copies of a full-length, T44A mutant form of the human gene. Under 12 hour light-12 hour dark (LD) and constant darkness (DD) conditions, wild-type transgenic (see Stock No. 022149) and mutant transgenic mice show similar and robust circadian rhythms of wheel-running activity. Free-running periods are significantly shorter in mutant transgenic animals compared with wild-type controls, however. Mutant transgenic mice have a circadian periodicity of 23.42 hours under constant dark conditions compared to 23.78 hours in wildtype controls. They also take significantly longer to re-entrain to a light-dark regime after two weeks of constant darkness.
Treatment of mutant transgenic mice with nitroglycerin (NTG) evokes peripheral mechanical and thermal hyperalgesia. Mechanical thresholds are significantly lower in the T44A mice than in wildtype controls, in a migraine-like phenotype. Mice are also more sensitive to thermal stimuli than wildtype siblings, with a significantly lower recovery from thermal hyperalgesia. Ninety minutes after NTG treatment (5 mg/kg, i.p.), females, but not males, show a significant reduction in latency to paw withdrawal from a heat source compared to wildtype. Transgenic mutant animals exhibit lower thresholds to induce cortical spreading depression (a wave of ionic disturbance thought to be similar to migraine aura) during which their arteries are abnormally dilated, as seen during migraine in humans.
Human BAC RP11-1376P16 containing the entire CSNK1D gene on a 190-kb genomic insert (Genbank accession number AC129510) was modified to carry a threonine to alanine mutation at amino acid 44 (T44A). An internal ribosome entry site (IRES) followed by an enhanced green fluorescent protein gene (EGFP) was also added to the carboxy terminus, but fluorescence has not been detected in the transgenic mice. The transgenic vector was introduced to C57BL/6 x SJL F1 embryos. Line 827, carrying 2-3 copies of the transgene was backcrossed for more than 10 generations to C57BL/6 by the donating laboratory.
|Expressed Gene||GFP, Green Fluorescent Protein,|
|Site of Expression||Brain|
|Allele Name||transgene insertion 827, Ying-Hui Fu|
|Allele Type||Transgenic (Reporter, Inserted expressed sequence, Humanized sequence)|
|Allele Synonym(s)||Tg(CSNK1D*,-EGFP)827Yfu; transgene insertion 827, Ying-Hui Fu|
|Gene Symbol and Name||Tg(CSNK1D*,-EGFP)827Yfu, transgene insertion 827, Ying-Hui Fu|
|Gene Synonym(s)||hCKIdelta-T44A H|
|Promoter||CSNK1D, casein kinase 1 delta, human|
|Expressed Gene||GFP, Green Fluorescent Protein,|
|Site of Expression||Brain|
|Strain of Origin||(C57BL/6 x SJL)F1|
|Molecular Note||The human BAC clone RP11-1376P16 containing the CSNK1D gene was targeted to generate a threonine-to-alanine alteration at amino acid 44 in the protein (T44A). An IRES-GFP cassette was also inserted after the stop codon of the CSNK1D gene. Six lines were generated with two of the lines, 827 and 859, being high expressers due to insertion of 2 to 3 copies of the transgene. Transgene expression was confirmed by RT-PCR of brain lysates. This is a representative record for the two high expressing lines.|
Hemizygotes are viable and fertile.
When using the B6.Cg-Tg(CSNK1D*,-EGFP)827Yfu/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #022148 in your Materials and Methods section.
|Hemizygous or non carrier for Tg(CSNK1D*,-EGFP)827Yfu|
We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
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|Frozen Mouse Embryo||$2,595.00 per straw or vial|
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