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 Generation N22+F0pN1 Generation Definitions   Donating Investigator Elena Zhukova,   University of California Los Angeles

Description
Mice heterozygous for this "G-InsKi" allele are viable and fertile. Human insulin expressed from this mutant allele retains full biological activity. Expression of human insulin is specific to gastrin-expressing cells (G cells of the antral stomach and some duodenum cells), and is released into portal circulation in response to the same meal-associated stimuli that control gastrin release. Heterozygous mice exhibit normal blood glucose levels, and toxic hypoglycemia is not observed. The donating investigators report that human insulin levels are sufficient to activate insulin signaling cascades in the liver but not in skeletal muscle. These mutant mice may be useful for diabetes and obesity research, specifically for studying the molecular and physiological mechanisms by which the hepatic action of transgenic insulin prolongs the survival of diabetic mice (e.g. Ins2^Akita mutant mice).

Development
The "G-InsKi" targeting vector was created with the 346-bp coding sequence of the human insulin cDNA (position +12 to +358) positioned upstream of bovine growth hormone polyA sequence followed by a (loxp-flanked PGKNeo selection cassette. This construct was inserted into exon 2 of the endogenous gene via electroporation into 129/SvJae-derived LW-1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into (C57BL/6 x BALB/c)F1 blastocysts, and the chimeric male offspring were bred to C57BL/6 females. Heterozygous mice were backcrossed to C57BL/6 for at least 20 generations prior to arrival at The Jackson Laboratory.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Phenotype

Phenotype Information

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.

Gast^tm1(INS)Ez/Gast⁺

        involves: 129S4/SvJae * C57BL/6

• homeostasis/metabolism phenotype
• abnormal insulin secretion
  • human insulin is secreted by cells located at the bottom of gastric glands of the antrum in response to ingested small peptides   (MGI Ref ID J:99270)
• improved glucose tolerance
  • blood glucose levels are about 30% lower 40 minutes after a peptone meal containing 25g/l glucose compared to wild-type mice; however treatment with glucose in the absence of peptone resulted in similar increases in blood glucose in heterozygotes and wild type mice   (MGI Ref ID J:99270)
  • heterozygotes are not resistant to streptozotocin-induced diabetes   (MGI Ref ID J:99270)
• increased circulating insulin level
  • gastric peptone instillation induces a 2.2-fold increase in circulating levels of human insulin after 40 minutes   (MGI Ref ID J:99270)
  • intragastic lavage of a proton pump inhibitor (omeprazole) induces a 2.3-fold increase in circulating levels of insulin after 4 days of treatment and treatment with both peptone and the proton pump inhibitor together increases blood insulin levels further   (MGI Ref ID J:99270)
• endocrine/exocrine gland phenotype
• abnormal insulin secretion
  • human insulin is secreted by cells located at the bottom of gastric glands of the antrum in response to ingested small peptides   (MGI Ref ID J:99270)

View Research Applications

Research Applications

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

Diabetes and Obesity Research
Hyperinsulinemia
Hypoinsulinemia
Impaired Insulin Processing
Insulin Receptors and Growth Factors
Type 1 Diabetes (IDDM)
Type 1 Diabetes (IDDM) Analysis Strains

Endocrine Deficiency Research
Pancreas Defects

Immunology and Inflammation Research
Autoimmunity
      Type 1 Diabetes

Research Tools
Endocrine Deficiency Research
Immunology and Inflammation Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Gasttm1(INS)Ez
Allele Name		targeted mutation 1, Elena Zhukova
Allele Type		Targeted (knock-in)
Common Name(s)		G-InsKi;
Mutation Made By		Elena Zhukova,   University of California Los Angeles
Strain of Origin		129S4/SvJae
ES Cell Line Name		LW1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Gast, gastrin
Chromosome		11
Gene Common Name(s)		GAS; PPG34;
Molecular Note		The human insulin cDNA, without the polyA sequence, and a floxed pgk-neo cassette were inserted into exon 2. The human insulin gene is thus placed under the control of the mouse gastrin promoter. [MGI Ref ID J:99270]

Genotyping

Genotyping Information

Genotyping Protocols

Gast^tm1(INS)Ez, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Lu YC; Sternini C; Rozengurt E; Zhukova E. 2005. Release of transgenic human insulin from gastric g cells: a novel approach for the amelioration of diabetes. Endocrinology 146(6):2610-9. [PubMed: 15731364]  [MGI Ref ID J:99270]

Additional References

Gast^tm1(INS)Ez related

Lu YC; Rozengurt E; Zhukova E. 2007. Transgenic insulin released from G cells preferentially signals in the liver. Biochem Biophys Res Commun 355(1):23-7. [PubMed: 17291451]  [MGI Ref ID J:118626]

Health & husbandry

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.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, the donating investigator breeds heterozygotes with C57BL/6 mice.

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

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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