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| These transgenic animals contain the Clockdelta19 mutation, under the control of a tetracycline-responsive promoter element (TRE; tetO). When hemizygotes are bred with another mouse expressing a (reverse) tetracycline-controlled transactivator protein (rtTA or tTA), transgene expression can be conditionally regulated with doxycycline. This strain may be useful in studies of the brain and circadian behavior. | |||||||||||||||
Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Donating Investigator Joseph Takahashi, Univ Texas Southwestern Medical Ctr Description
Homozygous transgenic mice are viable and fertile. These animals express the Clockdelta19 mutation under the control of a tetracycline-responsive promoter element (TRE; tetO). When hemizygotes are bred with another transgenic mouse expressing reverse tetracycline-controlled transactivator protein (rtTA) or tetracycline-controlled transactivator protein (tTA) under the regulation of tissue-specific promoters, transgene expression can be conditionally regulated in the appropriate tissue of the bitransgenic offspring with the tetracycline analog, doxycycline.Transgenic expression of the Clock gene in the suprachiasmatic nucleus and brain of mice regulates the period length of circadian locomotor rhythms. This dominant negative mutant transgene lengthens the period of circadian locomotor rhythms in mice, whereas overexpression of the wild-type transgene (Stock No. 008278) shortens the period. These effects can be inhibited by low doses of doxycyline in the drinking water. The effects of low, but not high, doses of doxycyline are completely reversible and lead to a rapid reactivation of the transgene.
These mice may be useful in studies of the brain and behavior in the mouse
When bred to a strain expressing tTA in brain (see Stock No. 008284 for example), this mutant mouse strain may be useful in studies of circadian behavior.
Development
ENU mutagenesis was used to create an A to T transversion at the third base position of the 5' splice donor site of intron 19. Resultant mRNA lacks exon 19 and deletes 51 amino acids in the carboxy terminus of the protein. A transgenic vector was designed to carry this full-length Clockdelta19 mutant gene downstream of a tetracycline-responsive promoter (TRE; tetO). The vector was introduced to fertilized CD1 oocytes. Transgene positive founders (line CL57) were backcrossed to C57BL/6J for more than ten generations by the donating laboratory.
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Strains carrying other alleles of Clock
002923 C57BL/6J-Clockm1Jt/J 008278 C57BL/6J-Tg(tetO-Clock)1Jt/J View Strains carrying other alleles of Clock (2 strains)
Strains carrying other alleles of tetO
View Strains carrying other alleles of tetO (36 strains)
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.Tg(Scg2-tTA)1Jt/0 Tg(tetO-Clockm1Jt)CL57Jt/0
involves: C57BL/6J * CD-1
- behavior/neurological phenotype
- abnormal circadian phase (MGI Ref ID J:120326)
- transgenic mice show significant effects on phase resetting and period lengthening effects on locomotor activity rhythms
- delayed circadian phase (MGI Ref ID J:120326)
- when given a 6 hour light pulse during subjective night (circadian time (CT) 12 and 17), mice exhibit a significantly larger phase delay when the transgenes are being expressed relative to delay displayed when under doxycycline suppression of transgene expression
- phase shift is larger when transgene expression is on compared to when expression is suppressed
- abnormal locomotor activity (MGI Ref ID J:120326)
- with transgene expression, mice display lengthening of locomotor activity rhythms
- prolonged circadian period (MGI Ref ID J:120326)
- when released into constant darkness, mice show a lengthened circadian period about 1 hour greater than wild-type
- when treated with doxycycline (2 mg/ml) in drinking water, circadian period is shortened within one day to 23.7 hours, not significantly different from wild-type period of 23.6 hours
- when these mice are treated with doxycycline for 3 weeks before removal, lengthening of circadian period is not immediate, but takes longer than 3 months to lengthen to the previously observed increased length
- treatment with 10 ug/ml doxycycline immediately switches off transgene expression, but reversal upon return to normal water is rapid, occurring within 2-3 days rather than >3 months at 2 mg/ml doxycycline; 100 ug/ml doxycycline is as effective in regulating transgene expression
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:
Clock relatedNeurobiology Research
Behavioral and Learning Defects
Circadian Rhythms
Neurobiology Research
Behavioral and Learning Defects
Circadian Rhythms
Reproductive Biology Research
Fertility Defects
| Allele Symbol | Tg(tetO-Clockm1Jt)CL57Jt | ||
|---|---|---|---|
| Allele Name | transgene insertion CL57, Joseph S Takahashi | ||
| Allele Type | Transgenic (random, expressed) | ||
| Common Name(s) |
tetO::Clock | ||
| Strain of Origin | CD-1 | ||
| Expressed Gene | Clock, circadian locomoter output cycles kaput, mouse, laboratory | ||
| Promoter | tetO, tet operator, | ||
| Molecular Note |
A transgenic vector was designed to carry the full-length Clock | ||
Genotyping Protocols
Tg(tetO-Clock) , Standard PCR
Helpful Links
Genotyping resources and troubleshooting
Hong HK; Chong JL; Song W; Song EJ; Jyawook AA; Schook AC; Ko CH; Takahashi JS. 2007. Inducible and reversible Clock gene expression in brain using the tTA system for the study of circadian behavior. PLoS Genet 3(2):e33. [PubMed: 17319750] [MGI Ref ID J:120326]
Colony Maintenance
Breeding & Husbandry When maintained as a live colony, hemizygotes may be bred.
| Pricing for USA, Canada and Mexico shipping destinations |
|
Animals Provided
Price (US dollars $) Cryorecovery Fee $1900.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
| Pricing for International shipping destinations |
|
Animals Provided
Price (US dollars $) Cryorecovery Fee $2470.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
| Standard Supply | Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
| Control | ||
|---|---|---|
| Noncarrier | ||
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
Purchasing Information
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| phone: | 207-288-6470 |
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