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 Background Strain C57BL/6 Donor Strain 129P2 via E14TG2a ES cell line Generation N?+3 Generation Definitions   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)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

Maturity-Onset Diabetes of the Young, Type 2; 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 provided by MGI

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

Gck^tm1Efr/Gck^tm1Efr

        involves: 129P2/OlaHsd * C57BL/6

• mortality/aging
• partial embryonic lethality during organogenesis
  • about 1/3 of mutant embryos are resorbed starting at E9.5   (MGI Ref ID J:28756)

View Research Applications

Research Applications

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

Gck^tm1Efr related

Developmental Biology Research
Postnatal Lethality
      Homozygous

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

Endocrine Deficiency Research
Pancreas Defects

Genes & Alleles

Gene & Allele Information provided by MGI

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)		FGQTL3; GK; GLK; GLUKA; HHF3; HK4; HKIV; HXKP; LGLK; 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

Gck^tm1Efr, Standard PCR
NEOTD (Generic Neo), Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

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

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.
• Genomic DNA is available for this strain from the Mouse DNA Resource.

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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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