Overview

Also Known As: Ucp1^-

These Ucp knockout mice are sensitive to cold temperatures, exhibit altered metabolism and are resistant to diet induced obesity when maintained at 20°C. This mutant mouse strain may be useful in studies of obesity, metabolic homeostasis, and adaptive thermogenesis.

Donating Investigator

Leslie P. Kozak, Polish Academy of Sciences

Genetic overview

Genetic Background	Generation
002448 129S1/SvImJ

Ucp1^tm1Kz

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Ucp1	uncoupling protein 1 (mitochondrial, proton carrier)

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Research Applications

Research Tools
Endocrine Deficiency Research
Internal/Organ Research
Cardiovascular Research
Diabetes and Obesity Research
Metabolism Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice that are homozygous for this knockout allele are viable and fertile, but exhibit sensitivity to cold temperatures. The Donating Investigator notes that homozygous offspring have increased survival rates to weaning age when maintained at 25°C to 28°C. No gene product (mRNA or protein) is detected by Northern or Western blot analysis of brown adipose tissue from homozygotes. When maintained at 20°C, homozygotes are resistant to diet induced obesity with reduced white fat depot weights, exhibit a 0.1-0.3°C higher body temperature, and a slightly lowered respiratory quotient compared to controls. Notably, when maintained at 27°C, homozygous mutant mice are no longer resistant to diet induced obesity and gain weight at a rate similar to wildtype controls. An increase in the number of brown adipocytes in the inguinal fat depots is observed in mutant mice maintained at 20°C, on either diet. Homozygotes have reduced levels of plasma fatty acids, circulating triglyceride levels, and T4 levels. Spleen cell numbers are reduced by approximately 3-fold, CD8 single positive cells are reduced to approximately half and CD4/CD8 double positive cells in both the spleen and thymus are increased in homozygous animals. Homozygotes have no heat production from brown adipose tissue. Mitochondria isolated from the muscles of cold-acclimated homozygotes display an increased total ATP production capacity, a metabolic shift for increased lipid oxidation and reduced carbohydrate catabolism capacity with a corresponding increased serum level of beta-hydroxybuterate, and decreased sensitivity to fatty acids as uncoupling agents. Mitochondria isolated from brown adipose tissue from homozygotes exhibit increased rate of reactive oxygen species (ROS) production when compared to wildtype controls. The Donating Investigator reports that mice carrying this allele are less cold sensitive on the C57BL/6 genetic background compared to the 129 genetic background.

Development

A targeting vector was used to replace a BamHI/BglII fragment carrying exon 2 and part of exon 3 with the neo^r gene thereby deleting an essential membrane-spanning domain. The construct was electroporated into 129S2/SvPas derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to 129Sv/ImJ mice, and then backcrossed to 129Sv/ImJ for 25 generations.
Upon arrival at The Jackson Laboratory, the mice were crossed to 129S1/SvImJ (Stock No. 002448) at least once to establish the colony.

Control Suggestions

Wild-type from the colony
002448 129S1/SvImJ

Additional Information

Considerations for Choosing Controls

Selected References

Enerback S; Jacobsson A; Simpson EM; Guerra C; Yamashita H; Harper ME ; Kozak LP. 1997. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese [see comments] Nature 387(6628):90-4PubMed: 9139827 MGI: J:40053

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Genetics

Ucp1^tm1Kz

Allele Symbol: Ucp1^tm1Kz

Allele Name	targeted mutation 1, Leslie Kozak
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Ucp1^tm1Kz; targeted mutation 1, Leslie Kozak
Gene Symbol and Name	Ucp1, uncoupling protein 1 (mitochondrial, proton carrier)
Gene Synonym(s)	AI385626; UCP; SLC25A7; expressed sequence AI385626; Uncp; Ucpa; Slc25a7; Ucp
Strain of Origin	129S2/SvPas
Chromosome	8
Molecular Note	All of exon 2 and a portion of exon 3 were replaced by a neomycin selection cassette. The deleted region encoded an essential transmembrane domain. Transcript was undetected in homozygous mutant mice via Northern blot analysis. Western blot analysis confirmed the absence of encoded protein.
Mutations Made By	Leslie Kozak, Polish Academy of Sciences

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Research Tools
- Metabolism Research
- Diabetes and Obesity Research
Endocrine Deficiency Research
- Adipose Defects
Internal/Organ Research
- Adipose Defects
Cardiovascular Research
- Other
  - altered fat metabolism
Diabetes and Obesity Research
- Obesity Without Diabetes
  - diet-induced, resistant
Metabolism Research
- Free Radical Research
- Lipid Metabolism

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Ucp1^tm1Kz/Ucp1^tm1Kz
B6.Cg-Ucp

adipose tissue phenotype

decreased white adipose tissue amount
- reduced weight of all white fat depots after a high-fat diet and exposure to 20^oC temperatures for 8 weeks

increased brown adipose tissue amount
- an increase in the number of brown adipocytes in the inguinal fat pad was observed at at 20^oC on a high-fat diet

cellular phenotype

abnormal mitochondrial physiology
- mitochondria exhibit an impaired response to free fatty acid-induced decoupling to a de-energized state; linoleic acid, lauric acid and stearic acid stimulation of mitochondria showed reduced rates of de-energization compared to controls as measured by protonmotive force and oxygen consumption
- otonmotive force and oxygen consumption

growth/size/body region phenotype

decreased body weight
- both groups of animals consumed similar amounts of food, indicating that the differences in body weight was not due to differences in energy intake
- temperature dependent; at 20^oC, animals did not gain weight as quickly as controls on a high-fat, high-sucrose diet, but at 27^oC, the differences in body weight between mutants and controls were indistiguishable

decreased susceptibility to diet-induced obesity
- at 20^oC on a high-fat diet

homeostasis/metabolism phenotype

abnormal lipid homeostasis
- blood levels of beta-hydroxybuterate were significantly higher in homozygous mice suggesting higher fat oxidation rates

decreased circulating free fatty acid level
- mice have reduced levels of plasma fatty acids relative to littermates at 20^oC

decreased circulating thyroxine level
- T4 leves were decreased

decreased circulating triglyceride level
- reduced levels in bloob

decreased respiratory quotient
- at 20^oC, the respiratory quotient (the ratio of the volume of CO2 produced to the volume of O2 consumed) is slightly reduced

decreased susceptibility to diet-induced obesity
- at 20^oC on a high-fat diet

impaired adaptive thermogenesis
- lost body core temperature rapidly upon exposure to cold temperatures

increased body temperature
- 0.1-0.3^oC higher than controls

increased circulating triiodothyronine level
- T3 levels were increased

Genotype: Ucp1^tm1Kz/Ucp1^tm1Kz
involves: 129S2/SvPas * C57BL/6J

cellular phenotype

abnormal mitochondrial physiology
- mitochondria do respond to free fatty acids by uncoupling to a de-energized state similar to controls
- mutant mitochondria have lost the high GDP-binding capacity and do not become energized in reposnse to it; instead, mutant mitochondria are in a perpetually energized state

Genotype: Ucp1^tm1Kz/Ucp1^tm1Kz
(129S1.Cg-Ucp x B6.Cg-Ucp)F1

cellular phenotype

abnormal mitochondrial physiology
- mitochondria exhibit an impaired response to free fatty acid-induced decoupling to a de-energized state; linoleic acid, lauric acid and stearic acid stimulation of mitochondria showed reduced rates of de-energization compared to controls as measured by protonmotive force and oxygen consumption
- otonmotive force and oxygen consumption

mammalian phenotype

homeostasis/metabolism phenotype
- Normal - maintained normal body temperature upon exposure to cold

The following phenotype relates to a compound genotype created using this strain

Genotype: Ucp1^tm1Kz/Ucp1^tm1Kz
involves: 129S2/SvPas

adipose tissue phenotype

increased brown adipose tissue amount
- mass of brown fat was greater in homozygous mice than in controls; thought to be due to increased deposition of triglyceride

growth/size/body region phenotype

decreased susceptibility to diet-induced obesity
- animals did not become obese on either a low-fat or a high-fat diet
- no changes were observed in the body mass, selected fat-pad mass or in total body triglyceride content
- normal food intake was observed

homeostasis/metabolism phenotype

abnormal oxygen consumption
- reduced oxygen consumption compared to controls was observed after treatment with a beta3-adrenergic agonist; resting oxygen consuption levels were similar to controls

abnormal physiological response to xenobiotic
- abnormal response to beta3-adrenergic stimulation by the CL 316,243 agonist

decreased oxygen consumption
- in CL316243-treated mice

decreased susceptibility to diet-induced obesity
- animals did not become obese on either a low-fat or a high-fat diet
- no changes were observed in the body mass, selected fat-pad mass or in total body triglyceride content
- normal food intake was observed

impaired adaptive thermogenesis
- increased sensitivity to cold temperatures; most homozygous mice could not sustain body temperature when exposed to cold

Genotype: Ucp1^tm1Kz/Ucp1^tm1Kz
129S1.Cg-Ucp

adipose tissue phenotype

increased brown adipose tissue amount
- increased brown adipose tissue depot weight

cellular phenotype

abnormal mitochondrial physiology
- comparable content of mitochondrial protein
- decreased cytochrome c oxidase activity
- increased mitochondrial glycerol-3-phosphate dehydrogenase activity
- mitochondria exhibit an impaired response to free fatty acid-induced decoupling to a de-energized state; linoleic acid, lauric acid and stearic acid stimulation of mitochondria showed reduced rates of de-energization compared to controls as measured by protonmotive force and oxygen consumption
- otonmotive force and oxygen consumption

homeostasis/metabolism phenotype

impaired adaptive thermogenesis
- lost body core temperature rapidly upon exposure to cold temperatures

References

Enerback S; Jacobsson A; Simpson EM; Guerra C; Yamashita H; Harper ME ; Kozak LP. 1997. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese [see comments] Nature 387(6628):90-4PubMed: 9139827 MGI: J:40053

Additional - Ucp1^tm1Kz related

Technical Support

Contact Technical Support

Genotyping Protocols
- Separated PCR: Ucp1^tm1Kzalternate2
- MELT: Ucp1^tm1Kz Alternate4
- SEPARATED MELT: Ucp1^tm1Kzalternate2 MCA
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as heterozygotes. Although homozygotes are viable and fertile, they exhibit increased sensitivity to cold temperatures. The Donating Investigator notes that there is better survival of homozygous to weaning age when mice are maintained at 25°C to 28°C.
- Additional Breeding and Husbandry Support
Citation
When using the Ucp1^- mouse strain in a publication, please cite the originating article(s) and include JAX stock #017476 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

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Cryorecovery - Pricing

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We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We 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.

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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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Also Known As: Ucp1-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Ucp1tm1Kz

Allele Symbol: Ucp1tm1Kz

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Ucp1tm1Kz/Ucp1tm1KzB6.Cg-Ucp

adipose tissue phenotype

cellular phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

Genotype: Ucp1tm1Kz/Ucp1tm1Kzinvolves: 129S2/SvPas * C57BL/6J

cellular phenotype

Genotype: Ucp1tm1Kz/Ucp1tm1Kz(129S1.Cg-Ucp x B6.Cg-Ucp)F1

cellular phenotype

mammalian phenotype

Genotype: Ucp1tm1Kz/Ucp1tm1Kzinvolves: 129S2/SvPas

adipose tissue phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

Genotype: Ucp1tm1Kz/Ucp1tm1Kz129S1.Cg-Ucp

adipose tissue phenotype

cellular phenotype

homeostasis/metabolism phenotype

References

Additional - Ucp1tm1Kz related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Also Known As: Ucp1^-

Ucp1^tm1Kz

Allele Symbol: Ucp1^tm1Kz

Genotype: Ucp1^tm1Kz/Ucp1^tm1Kz
B6.Cg-Ucp

Genotype: Ucp1^tm1Kz/Ucp1^tm1Kz
involves: 129S2/SvPas * C57BL/6J

Genotype: Ucp1^tm1Kz/Ucp1^tm1Kz
(129S1.Cg-Ucp x B6.Cg-Ucp)F1

Genotype: Ucp1^tm1Kz/Ucp1^tm1Kz
involves: 129S2/SvPas

Genotype: Ucp1^tm1Kz/Ucp1^tm1Kz
129S1.Cg-Ucp

Additional - Ucp1^tm1Kz related