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 Generation N15pN1 Generation Definitions   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. Abberant gene products (mRNA) are detected by RT-PCR and RACE analysis of brain total RNA. No gene product (protein) is detected in homozygous mutant mice by immunohistochemical staining of superchiasmatic nuclei sampled over a 24 hour period. Western blots of liver reveal a deletion mutant protein product is produced. When housed in constant darkness, homozygotes have a short circadian period initially, and then exhibit gradual loss of rhythmicity. Homozygotes exhibit phase shift responses to light. This mutant mouse strain may be useful in studies of circadian rhythm and sleep patterns.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
A targeting vector containing a PGKneo cassette was used to disrupt exon 5 and a portion of exon 6. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric male animals were crossed to 129/sv female mice, and then backcrossed to C57BL/6J for 10 generations.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Per2^tm1Drw allele

010832

129S-Per2tm1Drw/J

View Strains carrying   Per2^tm1Drw     (1 strain)

Strains carrying other alleles of Per2

016176	B6(Cg)-Tg(tetO-Per2)2Jt/J
006852	B6.129S6-Per2tm1Jt/J
003819	B6.Cg-Per2tm1Brd Tyrc-Brd/J

View Strains carrying other alleles of Per2     (3 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Advanced Sleep Phase Syndrome, Familial, 1; FASPS1   (PER2)

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.

Per2^tm1Drw/Per2^tm1Drw

        involves: 129/Sv

• behavior/neurological phenotype
• abnormal circadian temperature homeostasis
  • the acrophase of core temperature is phase-advanced compared to in wild-type mice   (MGI Ref ID J:95746)
• abnormal sleep pattern
  • at the midday 3-hour period, mice wake more than wild-type mice   (MGI Ref ID J:95746)
  • at midday, mice exhibit less REM sleep than wild-type mice   (MGI Ref ID J:95746)
  • during the 12-hour recovery after 6 hours of prolonged waking, mice exhibit less waking and more short wave sleep compared to similarly treated wild-type mice   (MGI Ref ID J:95746)
  • mice are awake more during the mid-third of the light period compared with wild-type mice   (MGI Ref ID J:95746)
• advanced circadian phase
  • the acrophase of core temperature is phase-advanced compared to in wild-type mice   (MGI Ref ID J:95746)
• arrhythmic circadian persistence
  • all mice become arrhythmic when transferred into dark-dark conditions although at different duration and extent of rhythm persistence   (MGI Ref ID J:69626)
• homeostasis/metabolism phenotype
• abnormal circadian temperature homeostasis
  • the acrophase of core temperature is phase-advanced compared to in wild-type mice   (MGI Ref ID J:95746)

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		Per2tm1Drw
Allele Name		targeted mutation 1, David R Weaver
Allele Type		Targeted (knock-out)
Common Name(s)		Per2-; Per2m; mPer2ldc;
Mutation Made By		Shin Yamazaki,   Vanderbilt University
Strain of Origin		129S4/SvJae
Gene Symbol and Name		Per2, period circadian clock 2
Chromosome		1
Gene Common Name(s)		FASPS; FASPS1; mKIAA0347; mPer2; rPER2;
Molecular Note		Exon 5 and a portion of exon 6 were replaced with a neomycin selection cassette. Several transcript forms produced from the targeted allele were identified in homozygous mutant mice via RT-PCR and RACE analyses of brain RNA. The different transcripts involved aberrant splicing of exon 4 to a pseudoexon in intron 4, to a cryptic splice site within neo, and to exon 7. In spite of the transcripts having in-frame regions, normal protein was undetected in by immunohistochemical staining of superchiasmatic nuclei over a 24 hour period. [MGI Ref ID J:69626]

Genotyping

Genotyping Information

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Bae K; Jin X; Maywood ES; Hastings MH; Reppert SM; Weaver DR. 2001. Differential Functions of mPer1, mPer2, and mPer3 in the SCN Circadian Clock. Neuron 30(2):525-36. [PubMed: 11395012]  [MGI Ref ID J:69626]

Additional References

Per2^tm1Drw related

Anea CB; Ali MI; Osmond JM; Sullivan JC; Stepp DW; Merloiu AM; Rudic RD. 2010. Matrix metalloproteinase 2 and 9 dysfunction underlie vascular stiffness in circadian clock mutant mice. Arterioscler Thromb Vasc Biol 30(12):2535-43. [PubMed: 20829506]  [MGI Ref ID J:182097]

Bae K; Lee K; Seo Y; Lee H; Kim D; Choi I. 2006. Differential effects of two period genes on the physiology and proteomic profiles of mouse anterior tibialis muscles. Mol Cells 22(3):275-84. [PubMed: 17202855]  [MGI Ref ID J:135910]

Beaule C; Swanstrom A; Leone MJ; Herzog ED. 2009. Circadian modulation of gene expression, but not glutamate uptake, in mouse and rat cortical astrocytes. PLoS One 4(10):e7476. [PubMed: 19829696]  [MGI Ref ID J:154095]

Chen R; Schirmer A; Lee Y; Lee H; Kumar V; Yoo SH; Takahashi JS; Lee C. 2009. Rhythmic PER abundance defines a critical nodal point for negative feedback within the circadian clock mechanism. Mol Cell 36(3):417-30. [PubMed: 19917250]  [MGI Ref ID J:154857]

Cheng B; Anea CB; Yao L; Chen F; Patel V; Merloiu A; Pati P; Caldwell RW; Fulton DJ; Rudic RD. 2011. Tissue-intrinsic dysfunction of circadian clock confers transplant arteriosclerosis. Proc Natl Acad Sci U S A 108(41):17147-52. [PubMed: 21969583]  [MGI Ref ID J:177448]

Cho YH; Kim D; Choi I; Bae K. 2011. Identification of transcriptional regulatory elements required for the Mup2 expression in circadian clock mutant mice. Biochem Biophys Res Commun 410(4):834-40. [PubMed: 21703244]  [MGI Ref ID J:174778]

Duong HA; Robles MS; Knutti D; Weitz CJ. 2011. A molecular mechanism for circadian clock negative feedback. Science 332(6036):1436-9. [PubMed: 21680841]  [MGI Ref ID J:173532]

Grimaldi B; Bellet MM; Katada S; Astarita G; Hirayama J; Amin RH; Granneman JG; Piomelli D; Leff T; Sassone-Corsi P. 2010. PER2 controls lipid metabolism by direct regulation of PPARgamma. Cell Metab 12(5):509-20. [PubMed: 21035761]  [MGI Ref ID J:167907]

Gumz ML; Stow LR; Lynch IJ; Greenlee MM; Rudin A; Cain BD; Weaver DR; Wingo CS. 2009. The circadian clock protein Period 1 regulates expression of the renal epithelial sodium channel in mice. J Clin Invest 119(8):2423-34. [PubMed: 19587447]  [MGI Ref ID J:152557]

Hoogerwerf WA; Shahinian VB; Cornelissen G; Halberg F; Bostwick J; Timm J; Bartell PA; Cassone VM. 2010. Rhythmic changes in colonic motility are regulated by period genes. Am J Physiol Gastrointest Liver Physiol 298(2):G143-50. [PubMed: 19926812]  [MGI Ref ID J:157491]

Jang YS; Lee MH; Lee SH; Bae K. 2011. Cu/Zn superoxide dismutase is differentially regulated in period gene-mutant mice. Biochem Biophys Res Commun 409(1):22-7. [PubMed: 21549097]  [MGI Ref ID J:172369]

Lamia KA; Storch KF; Weitz CJ. 2008. Physiological significance of a peripheral tissue circadian clock. Proc Natl Acad Sci U S A 105(39):15172-7. [PubMed: 18779586]  [MGI Ref ID J:141274]

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]

Lee C; Weaver DR; Reppert SM. 2004. Direct association between mouse PERIOD and CKIepsilon is critical for a functioning circadian clock. Mol Cell Biol 24(2):584-94. [PubMed: 14701732]  [MGI Ref ID J:87576]

Lee H; Chen R; Lee Y; Yoo S; Lee C. 2009. Essential roles of CKIdelta and CKIepsilon in the mammalian circadian clock. Proc Natl Acad Sci U S A 106(50):21359-64. [PubMed: 19948962]  [MGI Ref ID J:155524]

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]

Park N; Cheon S; Son GH; Cho S; Kim K. 2012. Chronic circadian disturbance by a shortened light-dark cycle increases mortality. Neurobiol Aging 33(6):1122.e11-22. [PubMed: 22154820]  [MGI Ref ID J:188320]

Pendergast JS; Friday RC; Yamazaki S. 2010. Distinct functions of Period2 and Period3 in the mouse circadian system revealed by in vitro analysis. PLoS One 5(1):e8552. [PubMed: 20072700]  [MGI Ref ID J:157236]

Pendergast JS; Friday RC; Yamazaki S. 2010. Photic entrainment of period mutant mice is predicted from their phase response curves. J Neurosci 30(36):12179-84. [PubMed: 20826680]  [MGI Ref ID J:164289]

Pendergast JS; Oda GA; Niswender KD; Yamazaki S. 2012. Period determination in the food-entrainable and methamphetamine-sensitive circadian oscillator(s). Proc Natl Acad Sci U S A 109(35):14218-23. [PubMed: 22891330]  [MGI Ref ID J:188577]

Qu X; Metz RP; Porter WW; Cassone VM; Earnest DJ. 2007. Disruption of clock gene expression alters responses of the aryl hydrocarbon receptor signaling pathway in the mouse mammary gland. Mol Pharmacol 72(5):1349-58. [PubMed: 17715397]  [MGI Ref ID J:147684]

Shiromani PJ; Xu M; Winston EM; Shiromani SN; Gerashchenko D; Weaver DR. 2004. Sleep rhythmicity and homeostasis in mice with targeted disruption of mPeriod genes. Am J Physiol Regul Integr Comp Physiol 287(1):R47-57. [PubMed: 15031135]  [MGI Ref ID J:95746]

Wang CY; Wen MS; Wang HW; Hsieh IC; Li Y; Liu PY; Lin FC; Liao JK. 2008. Increased vascular senescence and impaired endothelial progenitor cell function mediated by mutation of circadian gene Per2. Circulation 118(21):2166-73. [PubMed: 18981300]  [MGI Ref ID J:165618]

Xu Y; Toh KL; Jones CR; Shin JY; Fu YH; Ptacek LJ. 2007. Modeling of a human circadian mutation yields insights into clock regulation by PER2. Cell 128(1):59-70. [PubMed: 17218255]  [MGI Ref ID J:126404]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

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

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.

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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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