Mice that are homozygous for the targeted mutation (Per2tm1Brd) exhibit a shortened circadian period and a loss of persistent circadian rhythmicity when maintained in constant darkness. This mutant mouse strain may be useful in studies related to the regulation of the sleep-wake cycle.
Dr. Allan Bradley, Baylor College of Medicine
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display gross physical or behavioral abnormalities. A mutant transcript, if translated, would generate a protein with an 87 amino acid deletion. When maintained in constant darkness, two phenotypic components are exhibited: a shortened circadian period and a loss of persistent circadian rhythmicity. When housed under constant light, homozygotes exhibit normal activity rhythm but a period length of less than 24 hours. By 9-12 months of age, homozygous females exhibit low reproductive success and produce small litters when compared to wildtype. These mice also carry the recessive Tyrc-Brd mutation that, when homozygous, results in albino coat color. This mutant mouse strain may be useful in studies related to the regulation of the sleep-wake cycle.
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt two Per2 exons encoding half of the PAS B domain and the entire PAC subdomain. The construct was transfected into 129S7/SvEvBrd-Hprtb-m2 derived AB2.2 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6-Tyrc-Brd blastocysts. The resulting chimeric mice were bred with C57BL/6-Tyrc-Brd mice (also called C57BL/6Brd-Tyrc-Brd). The donating investigator reported that mutant mice were then backcrossed to C57BL/6-Tyrc-Brd mice for at least five generations. Mice homozygous for both the Per2tm1Brd targeted mutation on chromosome 1 and the the recessive Tyrc-Brd mutation on chromosome 7 were sent to The Jackson Laboratory Repository (see SNP notes below).
A 32 SNP (single nucleotide polymorphism) panel analysis, with markers covering all 19 chromosomes and the X chromosome, was performed on the rederived living colony at The Jackson Laboratory Repository. This revealed 3 markers (one on chromosome 1 and two on chromosome 15) that were not fixed for C57BL/6 allele-type. The marker on chromosome 1 appears to be fixed as homozygous for 129 allele-type. This marker is close to the Per2 locus and is likely to be original ES cell genome segregating with the Per2tm1Brd targeted mutation. The two markers on chromosome 15 (located at ~34 Mbp and ~58 Mbp) also appear to be fixed as homozygous for 129 allele-type. This may represent a large region of chromosome 15 that is fixed as homozygous for 129 allele-type.
|Allele Name||targeted mutation 1, Allan Bradley|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||Per2Brdm1; mPer2Brdm1; mPer2m|
|Gene Symbol and Name||Per2, period circadian clock 2|
|Gene Synonym(s)||FASPS; FASPS1; mKIAA0347; mPer2; rPER2|
|Strain of Origin||129S7/SvEvBrd-Hprt |
|Molecular Note||Two exons containing the most conserved region of the gene were replaced with PGK-neo cassette, resulting in the deletion of the PAC subdomain and half of the PAS B domain. RT-PCR and sequence analysis of mutant animals detected a mutant transcript with a predicted protein containing an 87 amino acid deletion.|
|Mutations Made By|| |
Dr. Allan Bradley, Baylor College of Medicine
|Allele Name||albino, Allan Bradley|
|Allele Synonym(s)||C57BL/6c-; cBrd|
|Gene Symbol and Name||Tyr, tyrosinase|
|Gene Synonym(s)||ATN; C; CMM8; OCA1; OCA1A; OCAIA; Oca1; SHEP3; albino; c; skc35; skc35; skin/coat color 35|
|Site of Expression||Melanocytes.|
|Strain of Origin||C57BL/6|
|Molecular Note||This mutation arose spontaneously in or around 1991 in the C57BL/6 colony of Dr. Alan Bradley. It has been used in linkage studies based on the location of the tyrosinase gene on Chr 7, and its phenotype is complemented by a tyrosinase mini-gene. Sequence analysis of exon 1 identified the same G-to-T transversion at nucleotide position 291 (G291T), resulting in replacement of arginine by leucine at amino acid position 77, that is present in the albino 2 Jackson allele. It reverts at a very low frequency (there were two incidences in the original colony between 1992 and 1995), resulting in black pups in otherwise albino litters.|
This strain originated on a B6;129S background and mice were backcrossed to C57BL/6-Tyrc-Brd mice (also called C57BL/6Brd-Tyrc-Brd) for several generations before being made homozygous for both the Per2tm1Brd targeted mutation on chromosome 1 and the the recessive Tyrc-Brd mutation on chromosome 7. When maintaining a live colony, homozygous mice may be bred together. By 9-12 months of age, homozygous females exhibit low reproductive success and produce small litters when compared to wildtype. These mice also carry the recessive Tyrc-Brd mutation that, when homozygous, results in albino coat color.
When using the mPer2Brdm1 mouse strain in a publication, please cite the originating article(s) and include JAX stock #003819 in your Materials and Methods section.
|Heterozygous for Per2<tm1Brd>|
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of
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Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
|Frozen Mouse Embryo||$2,595.00 per straw or vial|
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