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- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
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
Former Names B6.129-Ucp2tm1Lowl/J (Changed: 09-DEC-05 ) 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 Donating Investigator Bradford B. Lowell, Beth Israel Deaconess Med Cntr (Harvard) 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.In a recent study (Endocrinology, 2009, Epub Feb 26) it was found that homozygous mutant mice exhibit increased oxidative stress as well as impaired glucose-stimulated insulin secretion, a finding that contrasts from the initial phenotype description. In the publication, it was suggested that the difference could be attributed to the earlier studies being performed on mice with a mixed B6;129S4 genetic background. These later studies, mice on a congenic B6.129S4 genetic background were used.
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 | ||
Related Strains
Parkinson's Disease Models
View Parkinson's Disease Models (109 strains)
Additional Web Information
Visit the Parkinson's Disease Resource site for helpful information on Parkinson's and research resources.
Phenotype
Phenotype Information
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Ucp2tm1Lowl/Ucp2tm1Lowl
involves: 129S4/SvJae * C57BL/6
- cellular phenotype
- abnormal cellular respiration
- in situ measurement indicates an increase in reactive oxygen species production by nigral dopaminergic neurons as compared to control (MGI Ref ID J:96713)
- decreased mitochondrial proliferation
- EM analysis of dopaminergic neurons indicates a decrease in mitochondrial number (MGI Ref ID J:96713)
- increased susceptibility to dopaminergic neuron neurotoxicity
- MPTP treatment results in 62% loss of nigral dopaminergic neurons, approximately double the loss found in wild-type cells (MGI Ref ID J:96713)
- nervous system phenotype
- decreased dopamine level
- MPTP treatment results in significantly lower dopamine levels in the striatum as compared to control (MGI Ref ID J:96713)
- increased susceptibility to dopaminergic neuron neurotoxicity
- MPTP treatment results in 62% loss of nigral dopaminergic neurons, approximately double the loss found in wild-type cells (MGI Ref ID J:96713)
- homeostasis/metabolism phenotype
- decreased dopamine level
- MPTP treatment results in significantly lower dopamine levels in the striatum as compared to control (MGI Ref ID J:96713)
- increased susceptibility to dopaminergic neuron neurotoxicity
- MPTP treatment results in 62% loss of nigral dopaminergic neurons, approximately double the loss found in wild-type cells (MGI Ref ID J:96713)
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
Research Tools
Toxicology Research
Genes & Alleles
Gene & Allele Information provided by MGI
| 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 Med Cntr (Harvard) | ||
| 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
Ucp2tm1Lowl, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
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
Ucp2tm1Lowl relatedAndrews ZB; Erion DM; Beiler R; Choi CS; Shulman GI; Horvath TL. 2010. Uncoupling protein-2 decreases the lipogenic actions of ghrelin. Endocrinology 151(5):2078-86. [PubMed: 20189996] [MGI Ref ID J:160003]
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; Horvath TL. 2009. Uncoupling protein-2 regulates lifespan in mice. Am J Physiol Endocrinol Metab 296(4):E621-7. [PubMed: 19141680] [MGI Ref ID J:148135]
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]
Dalgaard LT. 2012. UCP2 mRNA expression is dependent on glucose metabolism in pancreatic islets. Biochem Biophys Res Commun 417(1):495-500. [PubMed: 22177951] [MGI Ref ID J:180296]
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]
Dietrich MO; Antunes C; Geliang G; Liu ZW; Borok E; Nie Y; Xu AW; Souza DO; Gao Q; Diano S; Gao XB; Horvath TL. 2010. Agrp neurons mediate Sirt1's action on the melanocortin system and energy balance: roles for Sirt1 in neuronal firing and synaptic plasticity. J Neurosci 30(35):11815-25. [PubMed: 20810901] [MGI Ref ID J:164001]
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]
Evans ZP; Palanisamy AP; Sutter AG; Ellett JD; Ramshesh VK; Attaway H; Schmidt MG; Schnellmann RG; Chavin KD. 2012. Mitochondrial uncoupling protein-2 deficiency protects steatotic mouse hepatocytes from hypoxia/reoxygenation. Am J Physiol Gastrointest Liver Physiol 302(3):G336-42. [PubMed: 22094601] [MGI Ref ID J:183315]
Haschemi A; Chin BY; Jeitler M; Esterbauer H; Wagner O; Bilban M; Otterbein LE. 2011. Carbon monoxide induced PPARgamma SUMOylation and UCP2 block inflammatory gene expression in macrophages. PLoS One 6(10):e26376. [PubMed: 22046279] [MGI Ref ID J:179711]
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]
Liu DQ; Guo YL; Bian Z; Chen YY; Chen X; Liu Y; Zhang CY; Zen K. 2010. Uncoupling protein-2 negatively regulates polymorphonuclear leukocytes chemotaxis via modulating [Ca2+] influx. Arterioscler Thromb Vasc Biol 30(3):575-81. [PubMed: 20032292] [MGI Ref ID J:172104]
Park D; Han CZ; Elliott MR; Kinchen JM; Trampont PC; Das S; Collins S; Lysiak JJ; Hoehn KL; Ravichandran KS. 2011. Continued clearance of apoptotic cells critically depends on the phagocyte Ucp2 protein. Nature 477(7363):220-4. [PubMed: 21857682] [MGI Ref ID J:176250]
Parker N; Vidal-Puig AJ; Azzu V; Brand MD. 2009. Dysregulation of glucose homeostasis in nicotinamide nucleotide transhydrogenase knockout mice is independent of uncoupling protein 2. Biochim Biophys Acta 1787(12):1451-7. [PubMed: 19539600] [MGI Ref ID J:153452]
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]
Pi J; Bai Y; Daniel KW; Liu D; Lyght O; Edelstein D; Brownlee M; Corkey BE; Collins S. 2009. Persistent oxidative stress due to absence of uncoupling protein 2 associated with impaired pancreatic beta-cell function. Endocrinology 150(7):3040-8. [PubMed: 19246534] [MGI Ref ID J:158189]
Sun XL; Liu Y; Dai T; Ding JH; Hu G. 2011. Uncoupling protein 2 knockout exacerbates depression-like behaviors in mice via enhancing inflammatory response. Neuroscience 192:507-14. [PubMed: 21729739] [MGI Ref ID J:176691]
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
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 When maintaining a live colony, these mice are bred as homozygotes.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2250.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Embryos
Price (US dollars $) Frozen Embryo $1600.00 Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryopreserved Embryos
Available to most shipping destinations1
This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. 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, please visit our Cryopreserved Embryos web page.
1 Shipments cannot be made to Australia due to Australian government import restrictions.
2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2925.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Embryos
Price (US dollars $) Frozen Embryo $2080.00 Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryopreserved Embryos
Available to most shipping destinations1
This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. 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, please visit our Cryopreserved Embryos web page.
1 Shipments cannot be made to Australia due to Australian government import restrictions.
2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
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Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
General Supply Notes
- Genomic DNA is available for this strain from the Mouse DNA Resource.
Control Information
| Control | ||
|---|---|---|
| 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.Ordering Information
JAX® Mice
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General Terms and Conditions
For Licensing and Use Restrictions view the link(s) below:
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Contact information
General inquiries regarding Terms of UseContracts Administration
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JAX® Mice, Products & Services Conditions of Use
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (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. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.No Warranty
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