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Allele Symbol: Chek1tm1Sany Name: checkpoint kinase 1 homolog (S. pombe); targeted mutation 1, Yolanda Sanchez Alteration at locus: Knockout |
Genetic Alterations:
Chek1 genomic
clones were isolated from the RPCI-22 (129S6/SvEvTac) mouse BAC library
(ResGen). (ResGen). An Xba I-Hind III fragment containing exons 2-6 was
cloned from BAC into the bluescript vector. Mutations were made in exon 5
to change the triplet encoding R156 to that of glutamine (the
corresponding SNP in hChek1). Silent mutations were also made nearby to
create an Nhe I site and a Kpn I site (not shown) to facilitate the
detection of targeted alleles. A neo cassette flanked by FRT sites was
then inserted between exons 4 and 5. The resulting construct was digested
with restriction enzymes to separate the modified Chek1 fragment from the
vector bone; the former was electroporated into mouse embryonic stem
cells.
Genotype Determination:
ES Cell Line: 129SvEvTac or 129S6
Phenotype:
Homozygous phenotype:
Heterozygous phenotype: The
heterozygous has no phenotype in the absence of challenge and have not
determined in the presence of challenge
Founder genetic background: 50% 129S6 and 50% BlackSwiss background
Strain genetic background: C57BL/6
Strain Development:
Since the ES cell was 129S6 and the
chimeras were crossed with BlackSwiss
females, the offspring carrying
the mutant Chek1 allele were 50% 129S6 and
50% BlackSwiss background.
After the first backcross to C57BL/6 the genetic
mix is 1/4 129S6, 1/4
BlackSwiss, 1/2 C57BL/6. After second backcross the
mice will be 1/8
129S6, 1/8 BlackSwiss, 3/4 C57BL/6. It is this generation
of animals
that was deposited to MMRRC. Donor notes no unusual breeding or
reproductive characteristics observed.
Donor: Yolanda Sanchez, Ph.D., Datrmouth Medical School
Primary Reference:
Sanchez Y; Wong C; Thoma RS; Richman R; Wu Z; Piwnica-Worms H ; Elledge SJ, Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25 , Science 1997 Sep 5;277(5331):1497-501 (Medline PMID: 9278511)
Lam MH; Liu Q; Elledge SJ; Rosen JM, Chk1 is haploinsufficient for multiple functions critical to tumor suppression., Cancer Cell 2004 Jul;6(1):45-59 (Medline PMID: 15261141)
Liu Q; Guntuku S; Cui XS; Matsuoka S; Cortez D; Tamai K; Luo G; Carattini-Rivera S; DeMayo F; Bradley A; Donehower LA; Elledge SJ, Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint., Genes Dev 2000 Jun 15;14(12):1448-59 (Medline PMID: 10859164)
Mice recovered from a cryo-archive will have health surveillance performed on the resuscitated animals.
Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.
Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.
Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.
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(Use the MMRRC Catalog Search to request more than one strain.) | |||||||
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Distribution Fee/unit (US $) |
Units | Notes | ||||
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Litter | Recovered litter1; additional fees for any special requests. | ||||
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Aliquot | Approximate quantity.2 | ||||
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Aliquot | Approximate quantity3: 20-40 embryos / aliquot | ||||
1 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one breedable mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.
2 An aliquot contains sufficient material (volume and concentration) for at least two IVF or several artificial inseminations (based on our procedures). The MMRRC makes no guarantee concerning success of these procedures when performed outside the MMRRC facilities.
3 An aliquot contains a sufficient number of embryos (in one or more vials and based on the transfer success rate of the MMRRC facility) to transfer to at least two recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.
To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the "Request this Strain" button above). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (International calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.
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Last Modified: April 18, 2011