Description

Strain Information

Former Names B6.129-Ucp2tm1Lowl/J    (Changed: 09-DEC-05 ) Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Bradford Lowell,   Beth Israel Deaconess Medical Center

Description
Homozygous mice are viable and fertile and do not express full length mRNA in heart, kidney, spleen, white adipose tissue, and pancreatic islets. In splenic mitochondria, endogenous protein was undetectable. When grown under high glucose conditions, cultured pancreatic islet cells from homozygous mice have increased insulin secretion and ATP levels compared to wildtype. Homozygous mice have 18% lower blood glucose levels. Whether fasting or fed, homozygotes have approximately 3-fold greater serum insulin due to increased insulin secretion. Similarly, glucose-stimulated insulin secretion is significantly increased. High fat diet-fed mice or palmitate-treated islets maintain pancreatic glucose responsiveness in vivo and in vitro compared to wildtype. Mitochondria isolated from the dopaminergic mesencephalic nigral cells of homozygous mice have increased reactive oxygen species but lesser mitochondria number and increased sensitivity to MPTP, mimicking Parkinson’s disease. This mouse may be useful in studies of diabetes, glucose-dependent metabolism-secretion coupling, aerobic respiration, Parkinson’s disease, epilepsy, stroke, and other neurodegenerative diseases.

Development
A targeting vector was created by replacing exons 3-7 of the endogenous gene with a PGK-Neo expression cassette. This construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and chimeric mice were bred to C57BL/6. The resulting heterozygotes were backcrossed to C57BL/6 mice for 10 generations before arrival at the The Jackson Laboratory.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

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.

Ucp2^tm1Lowl/Ucp2^tm1Lowl

        involves: 129S4/SvJae * C57BL/6

• cellular phenotype
• decreased mitochondrial proliferation (MGI Ref ID J:96713)
  • EM analysis of dopaminergic neurons indicates a decrease in mitochondrial number
• increased mitochondrial oxidation (MGI Ref ID J:96713)
  • in situ measurement indicates an increase in reactive oxygen species production by nigral dopaminergic neurons as compared to control
• nervous system phenotype
• decreased dopamine level (MGI Ref ID J:96713)
  • MPTP treatment results in significantly lower dopamine levels in the striatum as compared to control
• loss of dopaminergic neurons (MGI Ref ID J:96713)
  • MPTP treatment results in 62% loss of nigral dopaminergic neurons, approximately double the loss found in wild-type cells

View Research Applications

Research Applications

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

Diabetes and Obesity Research
Hyperinsulinemia
Hypoglycemia
Insulin Resistance (diet-induced)
Type 2 Diabetes (NIDDM) (diet-induced)

Metabolism Research
Free Radical Research
Lipid Metabolism

Neurobiology Research
Metabolic Defects
Neurodegeneration
Parkinson's Disease (increased vulnerability to MPTP)
Parkinson's Disease

Research Tools
Toxicology Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Ucp2tm1Lowl
Allele Name		targeted mutation 1, Bradford B Lowell
Allele Type		Targeted (knock-out)
Common Name(s)		Ucp2-;
Mutation Made By		Bradford Lowell,   Beth Israel Deaconess Medical Center
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Ucp2, uncoupling protein 2 (mitochondrial, proton carrier)
Chromosome		7
Gene Common Name(s)		BMIQ4; SLC25A8; UCPH;
Molecular Note		A PGK-neomycin resistance cassette replaced introns 2-7 including the start codon. Northern blot analysis using a full length rat cDNA probe did not detect intact mRNA in any tissues from homozygous mutant mice. Western blot analysis did not detect protein in spleen mitochondria from homozygous mutant mice. [MGI Ref ID J:75196]

Genotyping

Genotyping Information

Genotyping Protocols

Ucp2^tm1Lowl, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Zhang CY; Baffy G; Perret P; Krauss S; Peroni O; Grujic D; Hagen T; Vidal-Puig AJ; Boss O; Kim YB; Zheng XX; Wheeler MB; Shulman GI; Chan CB; Lowell BB. 2001. Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes. Cell 105(6):745-55. [PubMed: 11440717]  [MGI Ref ID J:75196]

Additional References

Ucp2^tm1Lowl related

Andrews ZB; Horvath B; Barnstable CJ; Elseworth J; Yang L; Beal MF; Roth RH; Matthews RT; Horvath TL. 2005. Uncoupling protein-2 is critical for nigral dopamine cell survival in a mouse model of Parkinson's disease. J Neurosci 25(1):184-91. [PubMed: 15634780]  [MGI Ref ID J:96713]

Andrews ZB; Liu ZW; Walllingford N; Erion DM; Borok E; Friedman JM; Tschop MH; Shanabrough M; Cline G; Shulman GI; Coppola A; Gao XB; Horvath TL; Diano S. 2008. UCP2 mediates ghrelin's action on NPY/AgRP neurons by lowering free radicals. Nature 454(7206):846-51. [PubMed: 18668043]  [MGI Ref ID J:139938]

Andrews ZB; Rivera A; Elsworth JD; Roth RH; Agnati L; Gago B; Abizaid A; Schwartz M; Fuxe K; Horvath TL. 2006. Uncoupling protein-2 promotes nigrostriatal dopamine neuronal function. Eur J Neurosci 24(1):32-6. [PubMed: 16882005]  [MGI Ref ID J:111552]

Baffy G; Zhang CY; Glickman JN; Lowell BB. 2002. Obesity-related fatty liver is unchanged in mice deficient for mitochondrial uncoupling protein 2. Hepatology 35(4):753-61. [PubMed: 11915020]  [MGI Ref ID J:106023]

Diao J; Allister EM; Koshkin V; Lee SC; Bhattacharjee A; Tang C; Giacca A; Chan CB; Wheeler MB. 2008. UCP2 is highly expressed in pancreatic alpha-cells and influences secretion and survival. Proc Natl Acad Sci U S A 105(33):12057-62. [PubMed: 18701716]  [MGI Ref ID J:138987]

Dietrich MO; Andrews ZB; Horvath TL. 2008. Exercise-induced synaptogenesis in the hippocampus is dependent on UCP2-regulated mitochondrial adaptation. J Neurosci 28(42):10766-71. [PubMed: 18923051]  [MGI Ref ID J:141085]

Evans ZP; Ellett JD; Schmidt MG; Schnellmann RG; Chavin KD. 2008. Mitochondrial uncoupling protein-2 mediates steatotic liver injury following ischemia/reperfusion. J Biol Chem 283(13):8573-9. [PubMed: 18086675]  [MGI Ref ID J:135165]

Joseph JW; Koshkin V; Saleh MC; Sivitz WI; Zhang CY; Lowell BB; Chan CB; Wheeler MB. 2004. Free fatty acid-induced beta-cell defects are dependent on uncoupling protein 2 expression. J Biol Chem 279(49):51049-56. [PubMed: 15448158]  [MGI Ref ID J:95203]

Krauss S; Zhang CY; Lowell BB. 2002. A significant portion of mitochondrial proton leak in intact thymocytes depends on expression of UCP2. Proc Natl Acad Sci U S A 99(1):118-22. [PubMed: 11756659]  [MGI Ref ID J:73708]

Krauss S; Zhang CY; Scorrano L; Dalgaard LT; St-Pierre J; Grey ST; Lowell BB. 2003. Superoxide-mediated activation of uncoupling protein 2 causes pancreatic beta cell dysfunction. J Clin Invest 112(12):1831-42. [PubMed: 14679178]  [MGI Ref ID J:118472]

Parton LE; Ye CP; Coppari R; Enriori PJ; Choi B; Zhang CY; Xu C; Vianna CR; Balthasar N; Lee CE; Elmquist JK; Cowley MA; Lowell BB. 2007. Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. Nature 449(7159):228-32. [PubMed: 17728716]  [MGI Ref ID J:125165]

Tsuboyama-Kasaoka N; Sano K; Shozawa C; Osaka T; Ezaki O. 2008. Studies of UCP2 transgenic and knockout mice reveal that liver UCP2 is not essential for the antiobesity effects of fish oil. Am J Physiol Endocrinol Metab 294(3):E600-6. [PubMed: 18089762]  [MGI Ref ID J:133468]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

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

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

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. 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.

Control Information

	Control
	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.

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.

---

Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

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.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

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.