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; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N25pN1 Generation Definitions   Donating Investigator Kosaku Uyeda,   Univ. of Texas Southwestern Medical Sch.

Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Mutant mice exhibit increased glucose and insulin levels, decreased free fatty acids, reduced epididymal and brown fat weight, and reductions in liver glycolysis and lipogenic enzymes. Mice fed diets high in sucrose or fructose died within one week most likely as a result of inhibited glycolysis. On a high starch diet, mice developed moderate insulin resistance and increased liver weight. This mutant mouse strain may be useful in studies of lipogenesis and glucose metabolism.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exons 12 through 14. The construct was electroporated into 129S6/SvEvTac derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6J for 25 generations. Upon arrival, mice were bred to C57BL/6J for at least 1 generation to establish the colony.

SNP (single nucleotide polymorphism) analysis performed by The Jackson Laboratory revealed that the Donating Investigator used C57BL/6N (4 of 5 markers segregating) in the development of the strain.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Williams-Beuren Syndrome; WBS   (MLXIPL)

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.

Mlxipl^tm1Kuy/Mlxipl^tm1Kuy

        involves: 129S6/SvEvTac * C57BL/6J

• mortality/aging
• increased sensitivity to induced morbidity/mortality
  • on a 70% sucrose diet homozygous mice die in less than 1 week   (MGI Ref ID J:89865)
  • on a high-fructose diet homozygous mice die within a few days   (MGI Ref ID J:89865)
  • on a standard chow diet homozygous mice have a normal life span   (MGI Ref ID J:89865)
• adipose tissue phenotype
• decreased brown adipose tissue amount
  • on a standard diet homozygous mice have lower brown fat weights   (MGI Ref ID J:89865)
• decreased epididymal fat pad weight
  • on a standard diet homozygous mice have lower epididymal fat weights   (MGI Ref ID J:89865)
• decreased white adipose tissue amount   (MGI Ref ID J:89865)
• homeostasis/metabolism phenotype
• abnormal glucose homeostasis   (MGI Ref ID J:89865)
• • increased circulating glucose level
    • plasma glucose levels are somewhat elevated   (MGI Ref ID J:89865)
  • increased circulating insulin level
    • plasma insulin levels are somewhat elevated   (MGI Ref ID J:89865)
    • on a high-starch diet plasma insulin levels increase significantly compared to homozygous mice on a standard diet or wild-type mice on either diet   (MGI Ref ID J:89865)
  • increased liver glycogen level
    • liver glycogen levels are elevated but muscle glycogen levels are not elevated   (MGI Ref ID J:89865)
    • liver glycogen levels are elevated further on a high-starch diet   (MGI Ref ID J:89865)
  • insulin resistance
    • on a high-starch diet homozygous mice are moderately insulin resistant   (MGI Ref ID J:89865)
• abnormal lipid homeostasis   (MGI Ref ID J:89865)
• • decreased circulating cholesterol level
    • on a high starch diet plasma cholesterol is significantly lower compared to wild-type mice on the same diet   (MGI Ref ID J:89865)
  • decreased fatty acid level
    • hepatic fatty acid synthesis rates are 65% lower in homozygous mice   (MGI Ref ID J:89865)
  • • decreased circulating free fatty acid level
      • on either a standard or high-starch diet plasma free fatty acid levels are about 50% that in wild-type mice on the same diet   (MGI Ref ID J:89865)
      • on a 70% sucrose diet free fatty acid levels decline further in homozygous mice   (MGI Ref ID J:89865)
• decreased body temperature
  • on a 70% sucrose diet homozygous mice develop hypothermia   (MGI Ref ID J:89865)
• liver/biliary system phenotype
• abnormal liver physiology
  • hepatic glucose levels are increased   (MGI Ref ID J:89865)
  • hepatic pyruvate/phosphoenolpyruvate ratio is decreased indicating inhibition of hepatic glycolysis   (MGI Ref ID J:89865)
• increased liver glycogen level
  • liver glycogen levels are elevated but muscle glycogen levels are not elevated   (MGI Ref ID J:89865)
  • liver glycogen levels are elevated further on a high-starch diet   (MGI Ref ID J:89865)
• increased liver weight
  • on a high starch diet liver weight are about 40% greater in homozygous mice compared to wild-type mice probably as a result of increased glycogen stores in homozygous mice   (MGI Ref ID J:89865)

View Research Applications

Research Applications

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

Diabetes and Obesity Research
Hyperglycemia
Hyperinsulinemia

Internal/Organ Research
Adipose Defects
Liver Defects

Metabolism Research
Enzyme Deficiency
Lipid Metabolism

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Mlxipltm1Kuy
Allele Name		targeted mutation 1, Kosaku Uyeda
Allele Type		Targeted (knock-out)
Common Name(s)		ChREBP-;
Mutation Made By		Kosaku Uyeda,   Univ. of Texas Southwestern Medical Sch.
Strain of Origin		129S6/SvEvTac
ES Cell Line Strain		129
Gene Symbol and Name		Mlxipl, MLX interacting protein-like
Chromosome		5
Gene Common Name(s)		CHREBP; MIO; MONDOB; WBSCR14; WS-bHLH; Wbscr14; Williams-Beuren syndrome chromosome region 14 homolog (human); bHLHd14;
Molecular Note		The genomic region spanning exons 12 - 14 was replaced with a neo cassette via homologous recombination. Real-time RT-PCR confirmed the absence of mRNA expression in homozygous mice. [MGI Ref ID J:89865]

Genotyping

Genotyping Information

Genotyping Protocols

Mlxipl^tm1Kuy SEP PCR, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Iizuka K; Bruick RK; Liang G; Horton JD; Uyeda K. 2004. Deficiency of carbohydrate response element-binding protein (ChREBP) reduces lipogenesis as well as glycolysis. Proc Natl Acad Sci U S A 101(19):7281-6. [PubMed: 15118080]  [MGI Ref ID J:89865]

Additional References

Mlxipl^tm1Kuy related

Burgess SC; Iizuka K; Jeoung NH; Harris RA; Kashiwaya Y; Veech RL; Kitazume T; Uyeda K. 2008. Carbohydrate-response element-binding protein deletion alters substrate utilization producing an energy-deficient liver. J Biol Chem 283(3):1670-8. [PubMed: 18042547]  [MGI Ref ID J:130720]

Cha JY; Repa JJ. 2007. The liver X receptor (LXR) and hepatic lipogenesis. The carbohydrate-response element-binding protein is a target gene of LXR. J Biol Chem 282(1):743-51. [PubMed: 17107947]  [MGI Ref ID J:154828]

Grefhorst A; Schreurs M; Oosterveer MH; Cortes VA; Havinga R; Herling AW; Reijngoud DJ; Groen AK; Kuipers F. 2010. Carbohydrate-response-element-binding protein (ChREBP) and not the liver X receptor alpha (LXRalpha) mediates elevated hepatic lipogenic gene expression in a mouse model of glycogen storage disease type 1. Biochem J 432(2):249-54. [PubMed: 20854262]  [MGI Ref ID J:167019]

Herman MA; Peroni OD; Villoria J; Schon MR; Abumrad NA; Bluher M; Klein S; Kahn BB. 2012. A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism. Nature 484(7394):333-8. [PubMed: 22466288]  [MGI Ref ID J:183854]

Iizuka K; Miller B; Uyeda K. 2006. Deficiency of carbohydrate-activated transcription factor ChREBP prevents obesity and improves plasma glucose control in leptin-deficient (ob/ob) mice. Am J Physiol Endocrinol Metab 291(2):E358-64. [PubMed: 16705063]  [MGI Ref ID J:111374]

Pashkov V; Huang J; Parameswara VK; Kedzierski W; Kurrasch DM; Tall GG; Esser V; Gerard RD; Uyeda K; Towle HC; Wilkie TM. 2011. Regulator of G Protein Signaling (RGS16) Inhibits Hepatic Fatty Acid Oxidation in a Carbohydrate Response Element-binding Protein (ChREBP)-dependent Manner. J Biol Chem 286(17):15116-25. [PubMed: 21357625]  [MGI Ref ID J:172091]

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, G200.

Colony Maintenance

Breeding & Husbandry	While maintaining a live colony, these mice are bred as homozygotes.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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