Overview

Also Known As:Prdm16^lox

Prdm16^lox/lox floxed mice may be useful for studying the role PRDM16 plays in the regulation of thermogenesis, obesity, and diabetes.

Donating Investigator

Bruce M Spiegelman, Dana-Farber Cancer Institute/Harvard Medical School

Genetic overview

Genetic Background	Generation

Prdm16^tm1.1Brsp

Allele Type	Gene Symbol	Gene Name
Targeted (Conditional ready (e.g. floxed), No functional change)	Prdm16	PR domain containing 16

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Research Applications

Internal/Organ Research
Metabolism Research
Diabetes and Obesity Research
Research Tools

View All Research Applications

Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

These Prdm16^lox/lox mutant mice possess loxP sites flanking exon 9 of the PR domain containing 16 (Prdm16) gene. PRDM16 is a transcriptional regulator involved in the differentiation of brown and beige adipose tissue. Brown adipose tissue (BAT) is metabolically active because it contains an abundance of mitochondria and mitochondrial uncoupling protein 1 (UCP1), which utilize glucose and lipids to produce ATP. ATP production in BAT has a role in thermogenesis and has anti-obesity/diabetes effects. Beige fat refers to a type of UCP1 positive cells that emerge in white fat depots under certain conditions, and has also been found to be involved in thermogenesis. PRDM16 is also involved in craniofacial development.
Homozygous Prdm16^lox/lox mice are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 9 deleted in the cre-expressing tissues.

For Example, when bred to B6;FVB-Tg(Adipoq-cre)1Evdr/J transgenic mice (Stock No. 010803), expressing Cre recombinase in adipocytes, Prdm16-deficient mice have ablated beige adipocyte function in subcutaneous fat following cold exposure or β3-adrenergic agonist treatment, and also reduced energy expenditure following β3-adrenergic agonist treatment. They develop obesity on a high-fat diet, with severe insulin resistance and hepatic steatosis. They showed altered fat distribution with an increase in subcutaneous adipose tissue, and acquired properties of visceral fat, including decreased thermogenic and increased inflammatory gene expression and increased macrophage accumulation.

Development

A targeting vector was designed to insert a loxP site upstream of exon 9 followed by a frt-flanked neomycin resistance (neo) cassette, and a second loxP site downstream of exon 9 of the PR domain containing 16 (Prdm16) gene. The construct was electroporated into 129Sv embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts and resulting chimeric mice were bred to C57BL/6 mice. Offspring were bred with Rosa26-Flp transgenic mice to delete the neo cassette, and progeny were crossed to remove the Flp-expressing transgene. These Prdm16^lox/lox mice were bred to C57BL/6J mice for at least 8 generations. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Cohen P; Levy JD; Zhang Y; Frontini A; Kolodin DP; Svensson KJ; Lo JC; Zeng X; Ye L; Khandekar MJ; Wu J; Gunawardana SC; Banks AS; Camporez JP; Jurczak MJ; Kajimura S; Piston DW; Mathis D; Cinti S; Shulman GI; Seale P; Spiegelman BM. 2014. Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cell 156(1-2):304-16PubMed: 24439384 MGI: J:208683

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Genetics

Prdm16^tm1.1Brsp

Allele Symbol: Prdm16^tm1.1Brsp

Allele Name	targeted mutation 1.1, Bruce M Spiegelman
Allele Type	Targeted (Conditional ready (e.g. floxed), No functional change)
Allele Synonym(s)	Prdm16^lox
Gene Symbol and Name	Prdm16, PR domain containing 16
Gene Synonym(s)
Strain of Origin	129/Sv
Chromosome	4
Molecular Note	The targeting vector was designed to insert a loxP site upstream of exon 9 followed by a frt-flanked neomycin resistance (neo) cassette, and a second loxP site downstream of exon 9.

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Internal/Organ Research
- Adipose Defects
Metabolism Research
- Lipid Metabolism
Diabetes and Obesity Research
Research Tools
- Cre-lox System
  - loxP-flanked Sequences
- Diabetes and Obesity Research
  - loxP

Mammalian Phenotype Terms by Genotype

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

Genotype: Prdm16^tm1.1Brsp/Prdm16^tm1.1Brsp Tg(Adipoq-cre)1Evdr/0
involves: 129/Sv * C57BL/6 * FVB/N

adipose tissue phenotype

increased total body fat amount
- body composition analysis after 16 weeks on high fat diet indicates increased fat mass with no change in lean body mass

decreased adipocyte glucose uptake
- glucose uptake is reduced in subcutaneous fat (79% decrease) and visceral fat (53% decrease) after 6 weeks on high fat diet as compared to controls

abnormal brown adipose tissue thermogenesis
- subcutaneous adipocytes exhibit a blunted response to stimuli such as isoproterenol that induce a thermogenic gene program (beige adipocytes)

increased subcutaneous adipose tissue amount
- subcutaneous fat mass from male mice after 16 weeks on high fat diet is increased to twice that of controls, epididymal and brown adipose tissue are unchanged

abnormal adipose tissue physiology
- O₂ consumption is reduced in subcutaneous adipose pads, but not in brown adipose pads, at baseline (36% reduced) and following stimulation with a beta-adrenergic agonist (49% reduced)

abnormal adipose tissue morphology
- subcutaneous adipose tissue from mice following 6 weeks on high fat diet has increased numbers of crown like structures, however, there are no changes in visceral (abdominal) fat
- subcutaneous adipose tisse from mice following 6 weeks on high fat diet has increased numbers of CD11b+F4/80+ macrophages
- subcutaneous adipose tissue contains larger adipocytes and fewer smaller multiocular UCP1+ adipocytes relative to control mice following cold exposure

abnormal adipose tissue distribution
- subcutaneous fat mass is doubled as compared to controls after 16 weeks on high fat diet; epididymal and BAT masses are unchanged

increased fat cell size
- subcutaneous adipocytes from male mice after 18 weeks on high fat diet exhibit a 33% increase in mean adipocyte area

cellular phenotype

decreased adipocyte glucose uptake
- glucose uptake is reduced in subcutaneous fat (79% decrease) and visceral fat (53% decrease) after 6 weeks on high fat diet as compared to controls

growth/size/body region phenotype

increased susceptibility to weight gain
- mice exhibit increased weight gain after 16 weeks on high-fat, high-carbohydrate diet relative to control mice

hematopoietic system phenotype

increased macrophage cell number
- subcutaneous adipose tissue from mice following 6 weeks on high fat diet has increased numbers of CD11b+F4/80+ macrophages, but macrophage numbers in visceral adipose tissue and spleen are unchanged

homeostasis/metabolism phenotype

insulin resistance
- clamped insulin levels do not increase as much as controls in mice after 6 weeks on high fat diet
- decreased whole body glucose uptake is observed in mice after 6 weeks on high fat diet
- a reduced glucose infusion rate (64% of controls) is observed in mice after 6 weeks on high fat diet

abnormal oxygen consumption
- unlike controls, mutant mice do not exhibit increased O₂ consumption following stimulation with a beta-adrenergic agonist

increased circulating insulin level
- increased fasting plasma insulin levels (55%) in mice after 6 weeks on high fat diet

increased respiratory quotient
- mice exhibit an increased respiratory exchange ratio (RER), but no increase in O₂ consumption

increased liver triglyceride level
- increased liver tryglycerides are observed in mice after 6 weeks on high fat diet as compared to controls

immune system phenotype

increased macrophage cell number
- subcutaneous adipose tissue from mice following 6 weeks on high fat diet has increased numbers of CD11b+F4/80+ macrophages, but macrophage numbers in visceral adipose tissue and spleen are unchanged

integument phenotype

increased subcutaneous adipose tissue amount
- subcutaneous fat mass from male mice after 16 weeks on high fat diet is increased to twice that of controls, epididymal and brown adipose tissue are unchanged

liver/biliary system phenotype

increased liver triglyceride level
- increased liver tryglycerides are observed in mice after 6 weeks on high fat diet as compared to controls

hepatic steatosis
- after 6 weeks on high fat diet

Genotype: Prdm16^tm1.1Brsp/Prdm16^tm1.1Brsp Myf5^tm1(cre)Mrc/Myf5⁺
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

cellular phenotype

abnormal cellular respiration
- reduced basal in interscapular brown adipose tissue

decreased mitochondrial number
- with poorly organized cristae in unstimulated interscapular brown adipose tissue

decreased mitochondrial DNA content
- in unstimulated interscapular brown adipose tissue

growth/size/body region phenotype

decreased lean body mass

decreased body length

decreased body weight
- at all ages

decreased body fat mass

homeostasis/metabolism phenotype

improved glucose tolerance

impaired adaptive thermogenesis
- precipitous drop in body temperature following exposure to cold

abnormal oxygen consumption

adipose tissue phenotype

increased brown fat cell lipid droplet size
- in the interscapular brown adipose tissue of mice older than 6 months

decreased brown fat lipid droplet number
- in the interscapular brown adipose tissue of mice older than 6 months

abnormal brown adipose tissue morphology
- Normal - however, tissue mass is not altered
- pale axillary and cervical brown adipose tissue depots

decreased body fat mass

abnormal interscapular fat pad morphology
- 3 week old mice fed a high-fat diet exhibit loss of normal brown adipocyte morphology unlike wild-type mice
- whitening in mice older than 6 months with increased size of the tissue, a switch from multilocular to unilocular morphology, and increased lipid content

abnormal brown adipose tissue thermogenesis
- precipitous drop in body temperature following exposure to cold
- Normal - however, diet-induced thermogenesis is normal

whitened brown adipose tissue morphology
- whitening in mice older than 6 months with increased size of the tissue, a switch from multilocular to unilocular morphology, and increased lipid content

increased interscapular fat pad weight
- Normal - however, juvenile mice exhibit normal sized brown adipose tissue depots
- in mice older than 6 months

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

Genotype: Prdm16^tm1.1Brsp/Prdm16^tm1.1Brsp
B6.129-Prdm16

normal phenotype

no abnormal phenotype detected
- mice are viable and fertile

References

Cohen P; Levy JD; Zhang Y; Frontini A; Kolodin DP; Svensson KJ; Lo JC; Zeng X; Ye L; Khandekar MJ; Wu J; Gunawardana SC; Banks AS; Camporez JP; Jurczak MJ; Kajimura S; Piston DW; Mathis D; Cinti S; Shulman GI; Seale P; Spiegelman BM. 2014. Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cell 156(1-2):304-16PubMed: 24439384 MGI: J:208683

Additional - Prdm16^tm1.1Brsp related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Prdm16 Alternate 3
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, homozygous mice may be bred together.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Homozygote
Citation
When using the Prdm16^lox mouse strain in a publication, please cite the originating article(s) and include JAX stock #024992 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

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Prdm16<tm1.1Brsp>

Related Products and Services

Frozen Mouse Embryo	B6.129-Prdm16<tm1.1Brsp>/J	$2595.00
Frozen Mouse Embryo	B6.129-Prdm16<tm1.1Brsp>/J	$2595.00
Frozen Mouse Embryo	B6.129-Prdm16<tm1.1Brsp>/J	$3373.50
Frozen Mouse Embryo	B6.129-Prdm16<tm1.1Brsp>/J	$3373.50

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:Prdm16lox

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Prdm16tm1.1Brsp

Allele Symbol: Prdm16tm1.1Brsp

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Prdm16tm1.1Brsp/Prdm16tm1.1Brsp Tg(Adipoq-cre)1Evdr/0involves: 129/Sv * C57BL/6 * FVB/N

adipose tissue phenotype

cellular phenotype

growth/size/body region phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

integument phenotype

liver/biliary system phenotype

Genotype: Prdm16tm1.1Brsp/Prdm16tm1.1Brsp Myf5tm1(cre)Mrc/Myf5+involves: 129S1/Sv * 129X1/SvJ * C57BL/6

cellular phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

adipose tissue phenotype

Genotype: Prdm16tm1.1Brsp/Prdm16tm1.1BrspB6.129-Prdm16

normal phenotype

References

Additional - Prdm16tm1.1Brsp related

Genotyping Protocols

Breeding Considerations

Mating System

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Also Known As:Prdm16^lox

Prdm16^tm1.1Brsp

Allele Symbol: Prdm16^tm1.1Brsp

Genotype: Prdm16^tm1.1Brsp/Prdm16^tm1.1Brsp Tg(Adipoq-cre)1Evdr/0
involves: 129/Sv * C57BL/6 * FVB/N

Genotype: Prdm16^tm1.1Brsp/Prdm16^tm1.1Brsp Myf5^tm1(cre)Mrc/Myf5⁺
involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Genotype: Prdm16^tm1.1Brsp/Prdm16^tm1.1Brsp
B6.129-Prdm16

Additional - Prdm16^tm1.1Brsp related