Overview

Exon 2 of these Chek1 (checkpoint kinase 1) targeted mutant mice is flanked by loxP sites. When crossed with a tissue-specific Cre strain, the exon is excised, enabling selective disruption of protein production. This conditional allele may be helpful in the development of anticancer drug therapies.

Donating Investigator

Dr. Stephen Elledge, Harvard University

Genetic overview

Genetic Background	Generation

Chek1^tm1Jmr

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Chek1	checkpoint kinase 1

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Research Applications

Research Tools
Cancer Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Chek1 (checkpoint kinase 1) is a haploinsufficient tumor suppressor gene that is essential for embryonic stem cell survival. CHEK1 null mice reportedly exhibit embryonic lethality at E6.5 due to a peri-implantation defect. Activated CHEK1 prevents cell cycle progression by inhibiting the cell cycle phosphatases Cdc25a and Cdc25c.

Exon 2 of these targeted mutant mice is flanked by loxP sites. When crossed with a tissue-specific Cre strain, the exon is excised, enabling selective disruption of protein production.

When bred to mice carrying Tg(Wap-cre)11738Mam (see Stock No. 008735 for example), Cre recombinase expression in the mammary gland results in proliferating cells that undergo apoptosis leading to developmental defects. Conditional heterozygosity increases the number of S phase cells and causes spontaneous DNA damage.

This conditional allele may be helpful in the development of anticancer drug therapies.

Development

A loxP-flanked neomycin cassette was ligated to a 2.2 kb exon 2-containing genomic fragment, of which the last 59 bp was replaced by an EcoRV and a loxP site. The targeting vector was introduced to 129-derived embryonic stem (ES) cells and the neomycin marker was excised through transient expression of Cre recombinase. This strain was backcrossed to C57BL/6 an estimated 5-6 times by the donating laboratory (see SNP note below).

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the first generation rederived living colony at The Jackson Laboratory Repository. Two of the 27 markers throughout the genome originated from an unknown source (chromosome 11 at ~8.40 Mbpand chromosome 13 at ~21.4 Mbp). In addition, all 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating, suggesting the mice sent to The Jackson Laboratory Repository were on a C57BL/6N genetic background.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Lam MH; Liu Q; Elledge SJ; Rosen JM. 2004. Chk1 is haploinsufficient for multiple functions critical to tumor suppression. Cancer Cell 6(1):45-59PubMed: 15261141 MGI: J:91266

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Genetics

Chek1^tm1Jmr

Allele Symbol: Chek1^tm1Jmr

Allele Name	targeted mutation 1, Jeffrey M Rosen
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	targeted mutation 1, Jeffrey M Rosen; Chek1^tm1Jmr
Gene Symbol and Name	Chek1, checkpoint kinase 1
Gene Synonym(s)	CHK1; expressed sequence C85740; C85740; Chk1
Strain of Origin	Not Specified
Chromosome	9
Molecular Note	LoxP sites were inserted around a 2.2kb genomic segment containing exon 2 via homologous recombination.
Mutations Made By	Dr. Jeffrey Rosen, Baylor College of Medicine

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Research Tools
- Cancer Research
  - anti-tumor activity
  - tumor immunology
- Cre-lox System
  - loxP-flanked Sequences
Cancer Research
- Tumor Suppressor Genes

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Chek1^tm1Jmr/Chek1^tm1Jmr Tg(Wap-cre)11738Mam/0
involves: C57BL/6

cellular phenotype

abnormal apoptosis
- about 10% - 12% is seen in the differentiating lobuloalveolar mammary epithelial cells compared to less than 1% in wild-type

decreased cell proliferation
- about 4% of cells in the mammary glands are proliferating at day 1 of lactation compared to 6.5% in wild-type

endocrine/exocrine gland phenotype

abnormal lactation
- females fail to nurse their young

abnormal mammary gland growth during pregnancy
- the number of lobuloalveolar mammary epithelial cells is reduced by 50% to 60% at day 1 of lactation in proportion to the number of cells expressing cre

integument phenotype

abnormal lactation
- females fail to nurse their young

abnormal mammary gland growth during pregnancy
- the number of lobuloalveolar mammary epithelial cells is reduced by 50% to 60% at day 1 of lactation in proportion to the number of cells expressing cre

reproductive system phenotype

abnormal mammary gland growth during pregnancy
- the number of lobuloalveolar mammary epithelial cells is reduced by 50% to 60% at day 1 of lactation in proportion to the number of cells expressing cre

Genotype: Chek1^tm1Jmr/Chek1⁺ Tg(Wap-cre)11738Mam/0
involves: C57BL/6

cellular phenotype

increased cell proliferation
- about 35% of cells in the mammary glands are proliferating at day 1 of lactation compared to 6.5% in wild-type

Genotype: Chek1^tm1Jmr/Chek1^tm1Jmr Tg(Tyr-cre)1Lru/Y
involves: C57BL/6 * DBA/2

integument phenotype

abnormal epidermal melanocyte morphology
- male mice show complete lack of epidermal melanocytes

abnormal hair follicle melanocyte morphology
- no DCT-expressing melanocytes are observed in the hair follicles, unlike in control mice

absent coat pigmentation
- adult male mice are completely devoid of coat pigmentation, unlike control mice

pigmentation phenotype

abnormal epidermal melanocyte morphology
- male mice show complete lack of epidermal melanocytes

abnormal hair follicle melanocyte morphology
- no DCT-expressing melanocytes are observed in the hair follicles, unlike in control mice

absent coat pigmentation
- adult male mice are completely devoid of coat pigmentation, unlike control mice

decreased melanocyte number
- adult males show a marked reduction or absence of neural crest-derived melanocytes in the eyes, unlike control mice
- Normal - however, males retain normal eye pigmentation in the retinal pigmented epithelium (RPE) due to inefficient transgene expression in the RPE

References

Lam MH; Liu Q; Elledge SJ; Rosen JM. 2004. Chk1 is haploinsufficient for multiple functions critical to tumor suppression. Cancer Cell 6(1):45-59PubMed: 15261141 MGI: J:91266

Additional - Chek1^tm1Jmr related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR:Chek1^tm1Jmr
- Genotyping resources and troubleshooting
Breeding Considerations

Heterozygous and homozygous floxed mice are viable and fertile.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129(Cg)-Chek1^tm1Jmr/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #019520 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous or Wildtype for Chek1<tm1Jmr>

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

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.

Related Products and Services

Frozen Mouse Embryo	B6.129(Cg)-Chek1<tm1Jmr>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129(Cg)-Chek1<tm1Jmr>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129(Cg)-Chek1<tm1Jmr>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129(Cg)-Chek1<tm1Jmr>/J Frozen Embryo	$3373.50

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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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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Chek1tm1Jmr

Allele Symbol: Chek1tm1Jmr

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Chek1tm1Jmr/Chek1tm1Jmr Tg(Wap-cre)11738Mam/0involves: C57BL/6

cellular phenotype

endocrine/exocrine gland phenotype

integument phenotype

reproductive system phenotype

Genotype: Chek1tm1Jmr/Chek1+ Tg(Wap-cre)11738Mam/0involves: C57BL/6

cellular phenotype

Genotype: Chek1tm1Jmr/Chek1tm1Jmr Tg(Tyr-cre)1Lru/Yinvolves: C57BL/6 * DBA/2

integument phenotype

pigmentation phenotype

References

Additional - Chek1tm1Jmr related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Chek1^tm1Jmr

Allele Symbol: Chek1^tm1Jmr

Genotype: Chek1^tm1Jmr/Chek1^tm1Jmr Tg(Wap-cre)11738Mam/0
involves: C57BL/6

Genotype: Chek1^tm1Jmr/Chek1⁺ Tg(Wap-cre)11738Mam/0
involves: C57BL/6

Genotype: Chek1^tm1Jmr/Chek1^tm1Jmr Tg(Tyr-cre)1Lru/Y
involves: C57BL/6 * DBA/2

Additional - Chek1^tm1Jmr related