Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C57BL/6 Donor Strain 129P2 via E14TG2a ES cell line Generation N?+3   Donating Investigator Shimon Efrat,   Sackler School of Medicine

Description
Glucokinase catalyzes a rate-limiting step in glucose metabolism in hepatocytes and pancreatic beta cells and is considered the "glucose sensor" for regulation of insulin secretion. Patients with maturity-onset diabetes of the young (MODY) have heterozygous point mutations in the glucokinase gene that result in reduced enzymatic activity and decreased insulin secretion. Disruption of the glucokinase gene results in a phenotype similar to MODY in heterozygous mice. These mice manifest a decreased insulin secretory response to glucose.

Related Strains

Strains carrying other alleles of Gck

003264

B6.129S7-Gcktm1Ts/J

View Strains carrying other alleles of Gck     (1 strain)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Maturity-Onset Diabetes of the Young, Type II; MODY2 - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Gck^tm1Efr/Gck⁺

        involves: 129P2/OlaHsd * C57BL/6

• homeostasis/metabolism phenotype
• abnormal glucose homeostasis (MGI Ref ID J:28756)
  • heterozygotes exhibit abnormal hepatic glucose metabolism: hyperglycemia and hyperinsulinemia reduce hepatic glucose production by only 47% vs 72% in wild-type mice
  • also, the fraction of hepatic UDPG pool derived from plasma glucose via the "direct" pathway is significantly reduced relative to wild-type
• hyperglycemia (MGI Ref ID J:28756)
  • at 5-6 months, heterozygous males show normoglycemia in the fed state
  • however, heterozygotes show a mild (25%) increase in overnight fasting glucose levels relative to wild-type mice
  • in contrast, plasma insulin levels remain unchanged relative to wild-type in both the fed and fasted state
• impaired glucose tolerance (MGI Ref ID J:28756)
  • heterozygotes display reduced tolerance to glucose relative to wild-type mice

Gck^tm1Efr/Gck^tm1Efr

        involves: 129P2/OlaHsd * C57BL/6

• lethality-prenatal/perinatal
• embryonic lethality during organogenesis (MGI Ref ID J:28756)
  • ~1/3 of mutant embryos are resorbed starting at E9.5

View Research Applications

Research Applications

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

Gck^tm1Efr related

Developmental Biology Research
Postnatal Mortality (Homozygous)

Diabetes and Obesity Research
Hyperglycemia
Hypoinsulinemia
Type 2 Diabetes (NIDDM)

Endocrine Deficiency Research
Pancreas Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Gcktm1Efr
Allele Name		targeted mutation 1, Shimon Efrat
Allele Type		Targeted (knock-out)
Common Name(s)		GK-;
Mutation Made By		Shimon Efrat,   Sackler School of Medicine
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		E14
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Gck, glucokinase
Chromosome		11
Gene Common Name(s)		GK; GLK; GLUKA; HHF3; HK4; HKIV; HXKP; MODY2; RNGK2; hexokinase 4;
Molecular Note		A fragment of the gene spanning exon 2 was replaced by a neomycin resistance cassette, resulting in a deletion and a frame shift of the transcript. Mice heterozygous for the targeted mutation had a 37% reduction in glucose phosphorylation activity in islet homogenates and a 28% reduction of activity in liver compared with wild-type littermates. [MGI Ref ID J:28756]

Genotyping

Genotyping Information

Genotyping Protocols

NEOTD (Generic Neo), STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Bali D; Svetlanov A; Lee HW; Fusco-DeMane D; Leiser M; Li B; Barzilai N; Surana M; Hou H; Fleischer N; DePinho R; Rossetti L; Efrat S. 1995. Animal model for maturity-onset diabetes of the young generated by disruption of the mouse glucokinase gene. J Biol Chem 270(37):21464-7. [PubMed: 7665557]  [MGI Ref ID J:28756]

Health & husbandry

Health & Colony Maintenance Information

Currently there no information available for this strain. This may be due to the supply level of this strain.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

General Terms and Conditions

See Terms of Use

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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Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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Terms of Use

Terms of Use

General Terms and Conditions

Use restrictions apply, see Policy on Licensing and Use Restrictions.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.