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 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 Western blot analysis of whole brain minus cerebellum and hypothalamus, whole hypothalamus, and anterior hypothalamus containing SCN, from homozygotes. Immunoprecipitation analysis of brain lysates from homozygotes does not detect any gene product (protein). Abberant gene products (mRNA) are detected by Northern blot analysis and RT-PCR, and have rhythmic expression. Under conditions of constant darkness, homozygous males exhibit a shorter free running period. A subset of mice exhibit progressive shortening of the period length in extended constant darkness. 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 3 and part of exon 4. 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 female 129/sv mice, and then backcrossed to C57BL/6J for 10 generations.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying   Per3^tm1Drw allele

010833

129S-Per3tm1Drw/J

View Strains carrying   Per3^tm1Drw     (1 strain)

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.

Per3^tm1Drw/Per3^tm1Drw

        involves: 129S4/SvJae

• behavior/neurological phenotype
• abnormal sleep pattern
  • during the 12-hour recovery after 6 hours of prolonged waking, mice exhibit less waking than similarly treated wild-type mice   (MGI Ref ID J:95746)
• shortened circadian period
  • homozygous male mice exhibited a shorter free running period when exposed to constant light; a subset of these mice continued to exhibit a shortening of period length progressive with time   (MGI Ref ID J:63933)
• nervous system phenotype
• abnormal brain wave pattern
  • recovery after 6 hours of prolonged waking, mice exhibit an increase in delta power lasting the first 6 hours of recovery sleep period compared with wild-type mice in which it lasts 3 hours   (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		Per3tm1Drw
Allele Name		targeted mutation 1, David R Weaver
Allele Type		Targeted (knock-out)
Common Name(s)		mPER3-deficient;
Mutation Made By		Shin Yamazaki,   Vanderbilt University
Strain of Origin		129S4/SvJae
Gene Symbol and Name		Per3, period circadian clock 3
Chromosome		4
Gene Common Name(s)		2810049O06Rik; GIG13; RIKEN cDNA 2810049O06 gene; mPer3; period3; rper3;
Molecular Note		The gene was disrupted by replacement of exon 3 and part of exon 4 (encoding amino acids 92-154) with a PGK-neo cassette via homologous recombination. Introduction of PGK-neo introduces stop codons into all 3 reading frames. Western blot analysis of brain lysates from homozygous mutant animals using antibodies directed against the C-terminus of the protein confirmed the absence of protein expression. Immunoprecipitation assays also confirmed the absence of protein product. Northern blot and RT-PCR analysis detected mutant transcripts containing neo and lacking exon 3 and part of exon 4 in brain and skeletal muscles from homozygous mutants. [MGI Ref ID J:63933]

Genotyping

Genotyping Information

Genotyping Protocols

Per3^tm1Drw, Robotic STD
Per3^tm1Drw, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

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]

Shearman LP; Jin X; Lee C; Reppert SM; Weaver DR. 2000. Targeted disruption of the mPer3 gene: subtle effects on circadian clock function. Mol Cell Biol 20(17):6269-75. [PubMed: 10938103]  [MGI Ref ID J:63933]

Additional References

Per3^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; 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]

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]

Costa MJ; So AY; Kaasik K; Krueger KC; Pillsbury ML; Fu YH; Ptacek LJ; Yamamoto KR; Feldman BJ. 2011. Circadian rhythm gene period 3 is an inhibitor of the adipocyte cell fate. J Biol Chem 286(11):9063-70. [PubMed: 21228270]  [MGI Ref ID J:170642]

Fogerty J; Besharse JC. 2011. 174delG mutation in mouse MFRP causes photoreceptor degeneration and RPE atrophy. Invest Ophthalmol Vis Sci 52(10):7256-66. [PubMed: 21810984]  [MGI Ref ID J:181596]

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]

Hasan S; van der Veen DR; Winsky-Sommerer R; Dijk DJ; Archer SN. 2011. Altered sleep and behavioral activity phenotypes in PER3-deficient mice. Am J Physiol Regul Integr Comp Physiol 301(6):R1821-30. [PubMed: 21957163]  [MGI Ref ID J:178770]

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]

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]

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]

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.

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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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