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

Former Names B6.129S4-Clocktm1.1Drw/J    (Changed: 11-FEB-10 ) 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 David R. Weaver,   Univ of Massachusetts Medical School

Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (protein) is detected by immunohistochemical and immunoprecipitation analysis of SCN (suprachiasma nucleus). Homozygotes exhibit a shorter circadian period of approximately 20 minutes, when kept in constant darkness. While under 12 hr light/12 hr dark (LD) cycle, homozygotes become active approximately 2 hours before the start of the dark cycle, indicating altered response to light cues. A four hour extended light period preceding constant darkness does not result in the expected activity rhythm phase delay. Re-entrainment with LD cycle followed by a 4 hour light pulse in the dark cycle does not cause activity rhythm phase advance.

Development
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 upstream of exon 5 of the targeted gene, and another loxP site was inserted downstream of exon 6. This construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells which were transiently transfected with a Cre recombinase vector to remove the selection cassette. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice, and then crossed to transgenic mice expressing Cre recombinase in the male germ line, to remove the floxed exons (Protamine-cre, on the C57BL6J background). Mice that no longer contained exons 5-6 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.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Clock

010490	B6.129S4-Clocktm1Rep/J
016167	B6.Cg-ClockGt(P007F12)Wrst/JtJ
016182	B6.Cg-Clocktm1Jt/J
008277	B6.Cg-Tg(tetO-Clockm1Jt)CL57Jt/J
016175	C.B6-Clockm1Jt/J
002923	C57BL/6J-Clockm1Jt/J
008278	C57BL/6J-Tg(tetO-Clock)1Jt/J

View Strains carrying other alleles of Clock     (7 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.

Clock^tm1.1Rep/Clock^tm1.1Rep

        involves: 129S4/SvJae * C57BL/6J

• behavior/neurological phenotype
• abnormal circadian phase
  • after light-dark entrainment for several weeks (L/D - 12/12 hours) followed by an extension of the light period by 4 hours, wild-type mice and heterozygotes exhibit a phase delay of ~1.6-1.9 hours whereas mutants don't show any delay   (MGI Ref ID J:109634)
• • advanced circadian phase
    • mutants become active ~ 2 hours before lights-off (start of dark cycle) while wild-type mice show activity at onset of dark period   (MGI Ref ID J:109634)
    • after LD entrainment for 3 weeks, exposure to a light pulse late in the dark phase followed by release into total darkness results in a phase advance of 6.8 hours compared to 1.8-2 hours exhibited by wild-type and heterozygotes in the same paradigm   (MGI Ref ID J:109634)

View Research Applications

Research Applications

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

Neurobiology Research
Circadian Rhythms

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Clocktm1.1Rep
Allele Name		targeted mutation 1.1, Steven M Reppert
Allele Type		Targeted (knock-out)
Common Name(s)		Clockdelta5-6; Clocktm1.1Drw;
Mutation Made By		Steven Reppert,   University of Massachusetts Medical Scho
Strain of Origin		129S4/SvJae
Gene Symbol and Name		Clock, circadian locomotor output cycles kaput
Chromosome		5
Gene Common Name(s)		5330400M04Rik; KAT13D; RIKEN cDNA 5330400M04 gene; bHLHe8; mKIAA0334;
Molecular Note		Cre mediated recombination resulted in the excision of exons 5 and 6. Immunohistochemistry confirmed absence of protein in mutants. [MGI Ref ID J:109634]

Genotyping

Genotyping Information

Genotyping Protocols

Clock^tm1.1Rep, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Debruyne JP; Noton E; Lambert CM; Maywood ES; Weaver DR; Reppert SM. 2006. A clock shock: mouse CLOCK is not required for circadian oscillator function. Neuron 50(3):465-77. [PubMed: 16675400]  [MGI Ref ID J:109634]

Additional References

Clock^tm1.1Rep related

Cretenet G; Le Clech M; Gachon F. 2010. Circadian clock-coordinated 12 Hr period rhythmic activation of the IRE1alpha pathway controls lipid metabolism in mouse liver. Cell Metab 11(1):47-57. [PubMed: 20074527]  [MGI Ref ID J:157002]

DeBruyne JP; Weaver DR; Reppert SM. 2007. CLOCK and NPAS2 have overlapping roles in the suprachiasmatic circadian clock. Nat Neurosci 10(5):543-5. [PubMed: 17417633]  [MGI Ref ID J:121658]

DeBruyne JP; Weaver DR; Reppert SM. 2007. Peripheral circadian oscillators require CLOCK. Curr Biol 17(14):R538-9. [PubMed: 17637349]  [MGI Ref ID J:123965]

Eckel-Mahan KL; Patel VR; Mohney RP; Vignola KS; Baldi P; Sassone-Corsi P. 2012. Coordination of the transcriptome and metabolome by the circadian clock. Proc Natl Acad Sci U S A 109(14):5541-6. [PubMed: 22431615]  [MGI Ref ID J:182655]

LeSauter J; Lambert CM; Robotham MR; Model Z; Silver R; Weaver DR. 2012. Antibodies for assessing circadian clock proteins in the rodent suprachiasmatic nucleus. PLoS One 7(4):e35938. [PubMed: 22558277]  [MGI Ref ID J:187275]

Masri S; Patel VR; Eckel-Mahan KL; Peleg S; Forne I; Ladurner AG; Baldi P; Imhof A; Sassone-Corsi P. 2013. Circadian acetylome reveals regulation of mitochondrial metabolic pathways. Proc Natl Acad Sci U S A 110(9):3339-44. [PubMed: 23341599]  [MGI Ref ID J:193829]

Peruquetti RL; de Mateo S; Sassone-Corsi P. 2012. Circadian proteins CLOCK and BMAL1 in the chromatoid body, a RNA processing granule of male germ cells. PLoS One 7(8):e42695. [PubMed: 22900038]  [MGI Ref ID J:189932]

Spengler ML; Kuropatwinski KK; Comas M; Gasparian AV; Fedtsova N; Gleiberman AS; Gitlin II; Artemicheva NM; Deluca KA; Gudkov AV; Antoch MP. 2012. Core circadian protein CLOCK is a positive regulator of NF-kappaB-mediated transcription. Proc Natl Acad Sci U S A 109(37):E2457-65. [PubMed: 22895791]  [MGI Ref ID J:189804]

Zuber AM; Centeno G; Pradervand S; Nikolaeva S; Maquelin L; Cardinaux L; Bonny O; Firsov D. 2009. Molecular clock is involved in predictive circadian adjustment of renal function. Proc Natl Acad Sci U S A 106(38):16523-8. [PubMed: 19805330]  [MGI Ref ID J:153224]

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 maintaining a live colony, these mice can be bred as homozygotes.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

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.

---

Ordering Information
JAX^® Mice
Surgical and Preconditioning Services
JAX^® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries regarding Terms of Use

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of mice, products or services, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and services by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or services by JACKSON.