Description

Strain Information

Former Names B6;129-Ucp3tm1Lowl/J    (Changed: 09-DEC-05 ) Type Mutant Stock; 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 skeletal muscle and brown adipose tissue. In skeletal muscle mitochondria, endogenous protein was undetectable. Skeletal muscle mitochondria from homozygous mice show decreased state 4 respiration. Further, skeletal muscle, but not liver, mitochondria produce more superoxide anions and reactive oxygen species both in vitro (lucigenin-derived chemiluminescence) and in vivo (aconitase activity). Skeletal muscle ATP synthesis under fasting conditions is approximately 4-fold greater in mutant mice. This mouse may be useful in studies of energy metabolism, thermogenesis, aerobic respiration (including mitochondrial respiration coupling), and age-related progressive deterioration of fatty acid homeostasis.

Development
A targeting vector was created by replacing exons 2-3 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 intercrossed for many generations before arrival at the The Jackson Laboratory. Upon arrival, these mice were bred to Stock No. 101043 (B6129SF1/J) for one generation and then maintained by heterozygous or homozygous matings.

Control Information

	Control
	101043 B6129SF1/J	(approximate)
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Ucp3^tm1Lowl/Ucp3^tm1Lowl

        involves: 129S4/SvJae * C57BL/6

• cellular phenotype
• abnormal aerobic energy metabolism (MGI Ref ID J:62313)
  • wild-type and mutant skeletal muscle displayed no differences in fatty acid or glucose oxidation at rest and post-exercise
  • in mutant skeletal muscle, mitochondria were more coupled (i.e. increased state 3/state 4 ratio); however, no alterations in whole animal oxygen consumption were observed
  • in mutant skeletal muscle, mutant mitochondria produced more reactive oxygen species (ROS) relative to wild-type
• increased mitochondrial oxidation (MGI Ref ID J:102104)
  • the mean ATP:ADP ratio in skeletal muscle of each individual mouse is significantly higher in 5-7 month old mutant mice than in age- and weight-matched controls, although the means for mutant and control groups do not differ significantly
  • the in vivo rate constant for ATP synthesis from P_i, determined using a combination of isotope labeling and NMR, in skeletal muscle is 2-fold greater in fasting 5-7 month old mutant mice than in age- and weight-matched controls
  • the rate of ATP synthesis in skeletal muscle of fasting 5-7 month old mutant mice, calculated from the rate constant and P_i concentration, is approximately 4-fold that in age- and weight-matched control mice
  • the in vivo index of mitochondrial coupling, calculated as the ratio of fasting ATP synthesis to tricarboxylic acid cycle (TCA) cycle flux rates, is 2-4-fold greater in skeletal muscle of mutant than of age- and weight-matched control mice; this presumably is due to the higher rate of ATP synthesis in mutant mice, as it was determined from the time course of glutamate C3 and C4 enrichment following infusion of [2-¹³C]acetate that the TCA flux rates are similar in skeletal muscle of fasting mutant and control mice
• growth/size phenotype
• *normal* growth/size phenotype (MGI Ref ID J:62313)
  • homozygotes were grossly normal and did not develop obesity
• homeostasis/metabolism phenotype
• *normal* homeostasis/metabolism phenotype (MGI Ref ID J:62313)
  • homozygotes showed no differences in body weight, triglyceride content or food intake relative to wild-type
  • homozygotes displayed normal physical performance during acute exercise relative to wild-type
  • only male homozygotes challenged with a high-fat diet tended to be heavier; however, this was not statistically significant
  • homozygotes displayed a normal thermogenic adaptation to cold
• increased fatty acid level (MGI Ref ID J:62313)
  • newborn (P4-P6 days) and young mutant mice (6 weeks) showed no differences in blood fatty acid levels relative to wild-type
  • older mutants (18-24-weeks) tended to have higher fatty acid levels in blood that reached statistical significance when challenged with a high-fat diet
  • the in vivo index of mitochondrial coupling, calculated as the ratio of fasting ATP synthesis to TCA cycle flux rates, is 2-4-fold greater in skeletal muscle of mutant than of age- and weight-matched control mice; this presumably is due to the higher rate of ATP synthesis in mutant mice, as it was determined from the time course of glutamate C3 and C4 enrichment following infusion of [2-¹³]acetate that the tricarboxylic acid cycle (TCA) flux rates are similar in skeletal muscle of fasting mutant and control mice

View Research Applications

Research Applications

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

Cardiovascular Research
Other (altered fat metabolism)

Cell Biology Research

Metabolism Research
Free Radical Research

Research Tools
Apoptosis Research
Metabolism Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Ucp3tm1Lowl
Allele Name		targeted mutation 1, Bradford B Lowell
Allele Type		Targeted (knock-out)
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		Ucp3, uncoupling protein 3 (mitochondrial, proton carrier)
Chromosome		7
Gene Common Name(s)		AI645527; SLC25A9; UCP-3; expressed sequence AI645527;
Molecular Note		A 700 bp genomic fragment containing part of exons 2 and 3 was replaced with a neomycin selection cassette. RNase protection analysis on RNA derived from skeletal muscle and brown adipose tissue of homozygous mice confirmed that no detectable transcriptwas expressed from this allele. Western blot analysis confirmed the absence of detectable protein in skeletal muscle mitochondria of homozygous mice. [MGI Ref ID J:62313]

Genotyping

Genotyping Information

Genotyping Protocols

Ucp3^tm1Lowl, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Vidal-Puig AJ; Grujic D; Zhang CY; Hagen T; Boss O; Ido Y; Szczepanik A; Wade J; Mootha V; Cortright R; Muoio DM; Lowell BB. 2000. Energy metabolism in uncoupling protein 3 gene knockout mice. J Biol Chem 275(21):16258-66. [PubMed: 10748196]  [MGI Ref ID J:62313]

Additional References

Ucp3^tm1Lowl related

Cline GW; Vidal-Puig AJ; Dufour S; Cadman KS; Lowell BB; Shulman GI. 2001. In vivo effects of uncoupling protein-3 gene disruption on mitochondrial energy metabolism. J Biol Chem 276(23):20240-4. [PubMed: 11274222]  [MGI Ref ID J:102104]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be 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
	101043 B6129SF1/J	(approximate)
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.

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Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
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Contact information

General inquiries

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fax:	207-288-6655

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