Description

Strain Information

Type Congenic; Mutant Strain; Transgenic; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Mating System Noncarrier x Hemizygote         (Female x Male) Species laboratory mouse Generation N10+ (06-NOV-08)   Donating Investigator Ajay Shah,   King's College London

Description
Mice hemizygous for the IGFBP-2 transgene are viable and fertile with no reported gross morphological or developmental changes. Transgenic mice overexpress human IGFBP-2 (hIGFBP-2), with hIGFBP-2 mRNA detected in a variety of organs and tissues, including adipose tissue. Overexpression of hIGFBP-2 is associated with reduced susceptibility to obesity and improved insulin sensitivity; transgenic mice are protected from glucose intolerance and increased blood pressure with age, and are also resistant to obesity and insulin resistance on a high fat diet. The phenotype of hIGFBP-2 overexpressing mice may vary between male and female mice. These IGFBP-2 transgenic mice may be useful in studying metabolic homeostasis, adipocyte biology, and the role of insulin-like growth factor binding protein in protecting against obesity- and age-associated complications (such as hypertension and diabetes).

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. As these mice were originally characterized on the FVB/N genetic background, it should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development
The IGFBP-2 transgene (isolated from a human cosmid clone) contains the entire structural human IGFBP2 gene. This 39 kb transgene was microinjected into the pronucleus of FVB/N embryos. Founder mice (line tg1) were bred to FVB/N mice. After this, IGFBP-2 transgenic mice were backcrossed to C57BL/6J mice for at least 9 generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were additionally backcrossed to C57BL/6J for at least one generation.

Control Information

	Control
	Noncarrier
	000664 C57BL/6J
Considerations for Choosing Controls

Phenotype

Phenotype Information

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.

Tg(IGFBP2)1Miel/0

        FVB/N-Tg(IGFBP2)1Miel

• growth/size phenotype
• increased resistance to diet-induced obesity (MGI Ref ID J:121961)
  • on high-fat diet for 32 weeks, mutants remain lean with no significant increase in size of fat depots, whereas wild-type mice have markedly increased size of fat depots when examined at 40 weeks
• weight gain (MGI Ref ID J:121961)
  • on a high-fat/high-calorie diet for 32 weeks from 8 weeks of age, mutants show attenuated weight gain relative to wild-type mice
• adipose tissue phenotype
• abnormal abdominal fat pad morphology (MGI Ref ID J:121961)
  • transgenic mice on high-fat diet for 32 weeks have significant reduction intraabdominal fat than wild-type mice; similarly, regular chow-fed mutants have less abdominal fat than diet-matched controls
• abnormal fat cell morphology (MGI Ref ID J:121961)
  • adipocytes are smaller than in wild-type mice, on both regular (1390 vs. 2100 um² mean cell area) and high-fat chow diets (2800 vs. 5900 um² mean cell area)
• decreased adipose tissue amount (MGI Ref ID J:121961)
  • on high-fat diet for 32 weeks, mutants have smaller fat depots than wild-type mice on the same diet when examined at 40 weeks
• cardiovascular system phenotype
• *normal* cardiovascular system phenotype (MGI Ref ID J:121961)
  • mutants are protected from age-related hypertension observed in aged wild-type mice
• decreased systolic blood pressure (MGI Ref ID J:121961)
  • wild-type mice at 40 weeks show increased systolic blood pressure compared to transgenic mice on both regular chow and high-fat diets
• liver/biliary system phenotype
• *normal* liver/biliary system phenotype (MGI Ref ID J:121961)
  • on high-fat diet for 32 weeks, mutants exhibit lower liver weight relative to controls when examined at 40 weeks
  • on high-fat diet for 32 weeks, mutants do not exhibit steatosis, whereas wild-type livers have macroscopic appearance compatible with increased fat content
• homeostasis/metabolism phenotype
• *normal* homeostasis/metabolism phenotype (MGI Ref ID J:121961)
  • at 8 weeks of age, blood glucose and insulin levels are similar to wild-type mice
  • insulin levels are similar to wild-type at 4-6 months of age
  • on high-fat diet, total energy intake is not significantly different from wild-type
• abnormal glucose homeostasis (MGI Ref ID J:121961)
  • in response to IGF-I, transgenic mice show an attenuated hypoglycemic response; plasma glucose levels decrease by ~half the value exhibited by wild-type mice
• abnormal circulating insulin level (MGI Ref ID J:121961)
  • in response to carbohydrate challenge, no siginificant increase in plasma insulin level is observed compared to elevated levels displayed by wild-type mice
• decreased circulating glucose level (MGI Ref ID J:121961)
  • by 4-6 months of age, transgenic mice display lower nonfasted glucose levels than wild-type littermates
  • increase in blood glucose of transgenic mice on high-fat diet is significantly blunted relative to wild-type
• improved glucose tolerance (MGI Ref ID J:121961)
  • mice are protected against the age-related decline in glucose tolerance displayed by wild-type mice between 8 and 40 weeks
  • on high-fat diet, transgenic mice are protected from development of glucose intolerance compared to wild-type
  • on both regular and high-fat diets, blood glucose of transgenic mice is significantly lower after glucose tolerance test than in wild-type
• increased insulin sensitivity (MGI Ref ID J:121961)
  • hypoglycemic response to exogenous insulin is greater in 40-week old mice compared to controls
• decreased circulating leptin level (MGI Ref ID J:121961)
  • leptin level increase is blunted in transgenic mice on high-fat diet, compared to wild-type
• decreased circulating triglyceride level (MGI Ref ID J:121961)
  • on high-fat diet, plasma triglyceride levels are significantly lower than in wild-type
• increased resistance to diet-induced obesity (MGI Ref ID J:121961)
  • on high-fat diet for 32 weeks, mutants remain lean with no significant increase in size of fat depots, whereas wild-type mice have markedly increased size of fat depots when examined at 40 weeks

Genes & Alleles

Gene & Allele Information

Allele Symbol		Tg(IGFBP2)1Miel
Allele Name		transgene insertion 1, John Miell
Allele Type		Transgenic (random, expressed)
Common Name(s)		line tg1;
Mutation Made By		John Miell,   University Hospital Lewisham
Strain of Origin		FVB/N
Expressed Gene		IGFBP2, insulin-like growth factor binding protein 2, 36kDa, human
Promoter		IGFBP2, insulin-like growth factor binding protein 2, 36kDa, human
Molecular Note		The IGFBP-2 transgene (isolated from a human cosmid clone) contains the entire structural human IGFBP2 gene. This 39 kb transgene was microinjected into the pronucleus of FVB/N embryos. Two lines tg1 and tg2 were established and line tg1 was analyzed in detail. [MGI Ref ID J:121961]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(IGFBP2)1Miel, STD PCR, vers. 1

Helpful Links

Genotyping resources and troubleshooting

References

References

Selected Reference(s)

Wheatcroft SB; Kearney MT; Shah AM; Ezzat VA; Miell JR; Modo M; Williams SC; Cawthorn WP; Medina-Gomez G; Vidal-Puig A; Sethi JK; Crossey PA. 2007. IGF-binding protein-2 protects against the development of obesity and insulin resistance. Diabetes 56(2):285-94. [PubMed: 17259371]  [MGI Ref ID J:121961]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           MGL375/MGL377

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, carrier mice may be bred to wildtype or C57BL/6J inbred mice.
Mating System	Noncarrier x Hemizygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of approximately nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within two business days following order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Noncarrier
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

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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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