Strain Name:

B6.129-Prdm16tm1.1Brsp/J

Stock Number:

024992

Availability:

In Progress

Register Interest
Prdm16lox/lox floxed mice may be useful for studying the role PRDM16 plays in the regulation of thermogenesis, obesity, and diabetes.

Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating Investigator Bruce Spiegelman,   Dana-Farber Cancer Institute

Description
These Prdm16lox/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 Prdm16lox/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 Prdm16lox/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 Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Prdm16
013100   FVB.C-Prdm16csp1/J
View Strains carrying other alleles of Prdm16     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Left Ventricular Noncompaction 8; LVNC8   (PRDM16)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Prdm16tm1.1Brsp/Prdm16tm1.1Brsp

        B6.129-Prdm16tm1.1Brsp
  • normal phenotype
  • no abnormal phenotype detected
    • mice are viable and fertile   (MGI Ref ID J:208683)

The following phenotype relates to a compound genotype created using this strain.
Contact JAX® Services jaxservices@jax.org for customized breeding options.

Prdm16tm1.1Brsp/Prdm16tm1.1Brsp Tg(Adipoq-cre)1Evdr/0

        involves: 129/Sv * C57BL/6 * FVB/N
  • adipose tissue phenotype
  • abnormal adipose tissue morphology
    • subcutaneous adipose tissue contains larger adipocytes and fewer smaller multiocular UCP1+ adipocytes relative to control mice following cold exposure   (MGI Ref ID J:208683)
    • 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   (MGI Ref ID J:208683)
    • subcutaneous adipose tisse from mice following 6 weeks on high fat diet has increased numbers of CD11b+F4/80+ macrophages   (MGI Ref ID J:208683)
    • 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   (MGI Ref ID J:208683)
    • increased fat cell size
      • subcutaneous adipocytes from male mice after 18 weeks on high fat diet exhibit a 33% increase in mean adipocyte area   (MGI Ref ID J:208683)
    • 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   (MGI Ref ID J:208683)
    • 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   (MGI Ref ID J:208683)
  • 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)   (MGI Ref ID J:208683)
    • abnormal 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   (MGI Ref ID J:208683)
    • abnormal brown adipose tissue thermogenesis
      • subcutaneous adipocytes exhibit a blunted response to stimuli such as isoproterenol that induce a thermogenic gene program (beige adipocytes)   (MGI Ref ID J:208683)
  • growth/size/body phenotype
  • increased susceptibility to weight gain
    • mice exhibit increased weight gain after 16 weeks on high-fat, high-carbohydrate diet relative to control mice   (MGI Ref ID J:208683)
  • 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   (MGI Ref ID J:208683)
  • 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   (MGI Ref ID J:208683)
  • homeostasis/metabolism phenotype
  • abnormal oxygen consumption
    • unlike controls, mutant mice do not exhibit increased O2 consumption following stimulation with a beta-adrenergic agonist   (MGI Ref ID J:208683)
  • increased circulating insulin level
    • increased fasting plasma insulin levels (55%) in mice after 6 weeks on high fat diet   (MGI Ref ID J:208683)
  • increased liver triglyceride level
    • increased liver tryglycerides are observed in mice after 6 weeks on high fat diet as compared to controls   (MGI Ref ID J:208683)
  • increased respiratory quotient
    • mice exhibit an increased respiratory exchange ratio (RER), but no increase in O2 consumption   (MGI Ref ID J:208683)
  • insulin resistance
    • a reduced glucose infusion rate (64% of controls) is observed in mice after 6 weeks on high fat diet   (MGI Ref ID J:208683)
    • decreased whole body glucose uptake is observed in mice after 6 weeks on high fat diet   (MGI Ref ID J:208683)
    • clamped insulin levels do not increase as much as controls in mice after 6 weeks on high fat diet   (MGI Ref ID J:208683)
  • 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   (MGI Ref ID J:208683)
  • 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   (MGI Ref ID J:208683)
  • liver/biliary system phenotype
  • hepatic steatosis
    • after 6 weeks on high fat diet   (MGI Ref ID J:208683)
  • increased liver triglyceride level
    • increased liver tryglycerides are observed in mice after 6 weeks on high fat diet as compared to controls   (MGI Ref ID J:208683)
View Research Applications

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

Diabetes and Obesity Research

Internal/Organ Research
Adipose Defects

Metabolism Research
Lipid Metabolism

Research Tools
Cre-lox System
      loxP-flanked Sequences
Diabetes and Obesity Research
      loxP

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Prdm16tm1.1Brsp
Allele Name targeted mutation 1.1, Bruce M Spiegelman
Allele Type Targeted (Conditional ready (e.g. floxed), No functional change)
Common Name(s) Prdm16lox;
Strain of Origin129/Sv
Gene Symbol and Name Prdm16, PR domain containing 16
Chromosome 4
Gene Common Name(s) 5730557K01Rik; CMD1LL; LVNC8; MEL1; PFM13; RIKEN cDNA 5730557K01 gene; cleft secondary palate 1; csp1; line 27;
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. [MGI Ref ID J:208683]

Genotyping

Genotyping Information


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

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):304-16. [PubMed: 24439384]  [MGI Ref ID J:208683]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice may be bred together.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


 

This strain is currently In Progress.

On 14-MAY-14 this strain was accepted for import and is now awaiting transfer to our campus.

Register Interest

View All Strains Awaiting Transfer from the Donor, In Progress and On Hold

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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