Strain Name:

STOCK Leprtm1Jke/J

Stock Number:

018989

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LeprloxTB mice only express the leptin receptor after Cre-mediated recombination.

Description

Strain Information

Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Mating SystemHeterozygote x Heterozygote         (Female x Male)   26-OCT-12
Specieslaboratory mouse
Generation?pN1+ (22-JAN-13)
Generation Definitions
 
Donating Investigator Joel K Elmquist,   UT Southwestern Med Center at Dallas

Description
These mice contain loxP flanked transcription blocker (loxTB) sequence between exons 16 and 17 of the leptin receptor (Lepr) gene, abolishing transcription of the exons downstream of the loxTB. Leptin is an adipose-derived hormone that acts to regulate food intake, energy expenditure, and body weight. LeprloxTB mice, lacking the long (B) isoform of the leptin receptor, are obese, hyperglycemic, and hyperinsulinemic, and have reduced energy expenditure. Mice that are heterozygous for the targeted mutation are viable and fertile, while homozygous mice are infertile. When these mutant mice are bred to mice that express Cre recombinase, the resulting offspring will have the loxTB removed and Lepr expression will be restored in cre expressing cells.

For example, when bred to STOCK Tg(Pomc1-cre)16Lowl/J mice (Stock No. 005965) expressing Cre-recombinase in proopiomelanocortin (POMC) neurons, the resulting offspring have normal glucose and glucagon levels. They have moderately restored energy expenditure and body weight, with no reduction on food intake.

Development
A targeting vector was used to insert a loxP flanked transcription blocker (loxTB), containing multiple polyadenylation signals and a neomycin resistance cassette (neo), between exons 16 and 17 of the leptin receptor (Lepr) gene. The construct was electroporated into 129X1-derived embryonic stem (ES) cells and correctly targeted ES cells were injected into C57BL/6Jrecipient blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice and were subsequently crossed to FVB. These LeprloxTB mice were maintained on a mixed background. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Control Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying other alleles of Lepr     (19 strains)

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.
Leptin Receptor Deficiency   (LEPR)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

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

Leprtm1Jke/Leprtm1Jke

        involves: 129X1/SvJ * C57BL/6J
  • homeostasis/metabolism phenotype
  • abnormal glucose homeostasis
    • insulin-stimulated glucose disposal is impaired compared to in wild-type mice   (MGI Ref ID J:184572)
    • abnormal gluconeogenesis
      • basal and insulin-stimulated   (MGI Ref ID J:184572)
    • hyperglycemia   (MGI Ref ID J:184572)
    • increased circulating glucagon level
      • in male mice at 12 and 20 weeks in the fed, fasted and carbohydrate-refed condition   (MGI Ref ID J:184572)
    • increased circulating insulin level   (MGI Ref ID J:184572)
    • increased insulin secretion
      • in the pancreas   (MGI Ref ID J:184572)
    • increased insulin sensitivity   (MGI Ref ID J:184572)
  • decreased carbon dioxide production   (MGI Ref ID J:184572)
  • decreased oxygen consumption   (MGI Ref ID J:184572)
  • decreased respiratory quotient   (MGI Ref ID J:184572)
  • increased circulating cholesterol level   (MGI Ref ID J:184572)
  • increased circulating leptin level   (MGI Ref ID J:184572)
  • increased circulating triglyceride level   (MGI Ref ID J:184572)
  • increased liver triglyceride level   (MGI Ref ID J:184572)
  • behavior/neurological phenotype
  • abnormal eating behavior   (MGI Ref ID J:184572)
  • hypoactivity
    • during the dark phase   (MGI Ref ID J:184572)
  • growth/size/body phenotype
  • obese   (MGI Ref ID J:184572)
  • endocrine/exocrine gland phenotype
  • increased insulin secretion
    • in the pancreas   (MGI Ref ID J:184572)
  • liver/biliary system phenotype
  • increased liver triglyceride level   (MGI Ref ID J:184572)

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

Leprtm1Jke/Leprtm1Jke Tg(Pomc1-cre)16Lowl/0

        involves: 129X1/SvJ * C57BL/6J * FVB/N   (conditional)
  • homeostasis/metabolism phenotype
  • *normal* homeostasis/metabolism phenotype
    • mice exhibit normal circulating glucagon levels in the fed and carbohydrate-refed state   (MGI Ref ID J:184572)
    • abnormal glucose homeostasis
      • mice exhibit normal basal glucose turnover compared with Leprtm1Jke homozygotes   (MGI Ref ID J:184572)
      • insulin-stimulated glucose disposal is impaired compared to in wild-type mice   (MGI Ref ID J:184572)
      • however, mice exhibit normal circulating glucose levels at 6, 8 and 12 weeks   (MGI Ref ID J:184572)
      • decreased circulating glucose level
        • compared with Leprtm1Jke homozygotes   (MGI Ref ID J:184572)
      • decreased circulating insulin level
        • at 8 and 12 weeks compared with Leprtm1Jke homozygotes   (MGI Ref ID J:184572)
      • increased circulating insulin level
        • compared with wild-type mice   (MGI Ref ID J:184572)
      • increased insulin secretion
        • in the pancreas compared with wild-type mice   (MGI Ref ID J:184572)
      • increased insulin sensitivity
        • compared with Leprtm1Jke homozygotes   (MGI Ref ID J:184572)
    • decreased carbon dioxide production
      • compared with wild-type mice   (MGI Ref ID J:184572)
    • decreased circulating cholesterol level
      • compared with Leprtm1Jke homozygotes   (MGI Ref ID J:184572)
    • decreased circulating triglyceride level
      • compared with Leprtm1Jke homozygotes   (MGI Ref ID J:184572)
    • decreased liver triglyceride level
      • compared with Leprtm1Jke homozygotes   (MGI Ref ID J:184572)
    • decreased oxygen consumption
      • compared with wild-type mice   (MGI Ref ID J:184572)
    • increased carbon dioxide production
      • compared with Leprtm1Jke homozygotes   (MGI Ref ID J:184572)
    • increased circulating cholesterol level
      • compared with wild-type mice   (MGI Ref ID J:184572)
    • increased circulating leptin level
      • compared with wild-type mice   (MGI Ref ID J:184572)
    • increased circulating triglyceride level
      • compared with wild-type mice   (MGI Ref ID J:184572)
    • increased liver triglyceride level
      • compared with wild-type mice   (MGI Ref ID J:184572)
    • increased oxygen consumption
      • compared with Leprtm1Jke homozygotes   (MGI Ref ID J:184572)
    • increased respiratory quotient
      • compared with wild-type mice   (MGI Ref ID J:184572)
  • growth/size/body phenotype
  • decreased body weight
    • in male mice after 12 weeks compared with Leprtm1Jke homozygotes   (MGI Ref ID J:184572)
  • decreased total body fat amount
    • in male mice at 20 weeks compared with Leprtm1Jke homozygotes   (MGI Ref ID J:184572)
  • increased total body fat amount
    • in male mice at 12 and 20 weeks compared with wild-type mice   (MGI Ref ID J:184572)
  • obese
    • in male mice between 4 and 12 weeks less severe after 12 weeks compared with wild-type mice   (MGI Ref ID J:184572)
    • in female mice   (MGI Ref ID J:184572)
  • behavior/neurological phenotype
  • abnormal eating behavior
    • compared with wild-type mice   (MGI Ref ID J:184572)
  • hyperactivity
    • during the dark phase compared with wild-type mice   (MGI Ref ID J:184572)
  • adipose tissue phenotype
  • decreased total body fat amount
    • in male mice at 20 weeks compared with Leprtm1Jke homozygotes   (MGI Ref ID J:184572)
  • increased total body fat amount
    • in male mice at 12 and 20 weeks compared with wild-type mice   (MGI Ref ID J:184572)
  • endocrine/exocrine gland phenotype
  • increased insulin secretion
    • in the pancreas compared with wild-type mice   (MGI Ref ID J:184572)
  • liver/biliary system phenotype
  • decreased liver triglyceride level
    • compared with Leprtm1Jke homozygotes   (MGI Ref ID J:184572)
  • increased liver triglyceride level
    • compared with wild-type mice   (MGI Ref ID J:184572)
View Research Applications

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

Diabetes and Obesity Research
Hyperglycemia
Hyperinsulinemia
      obesity, severe, due to leptin deficiency (rare)
Impaired Insulin Processing

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

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Leprtm1Jke
Allele Name targeted mutation 1, Joel K Elmquist
Allele Type Targeted (Null/Knockout)
Common Name(s) LeprloxTB;
Mutation Made By Joel Elmquist,   UT Southwestern Med Center at Dallas
Strain of Origin129X1/SvJ
Gene Symbol and Name Lepr, leptin receptor
Chromosome 4
Gene Common Name(s) CD295; Fa; LEP-R; LEPRD; LEPROT; Leprb; Modb1; OB-R; OB-RGRP; OBR; db; diabetes; leptin receptor gene-related protein; obese-like; obl;
Molecular Note A floxed transcription blocker was inserted into intron 16. [MGI Ref ID J:184572]

Genotyping

Genotyping Information

Genotyping Protocols

Leprtm1Jke,

Separated MCA


Leprtm1Jke, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Berglund ED; Vianna CR; Donato J Jr; Kim MH; Chuang JC; Lee CE; Lauzon DA; Lin P; Brule LJ; Scott MM; Coppari R; Elmquist JK. 2012. Direct leptin action on POMC neurons regulates glucose homeostasis and hepatic insulin sensitivity in mice. J Clin Invest 122(3):1000-9. [PubMed: 22326958]  [MGI Ref ID J:184572]

Additional References

Leprtm1Jke related

Elias CF. 2014. A critical view of the use of genetic tools to unveil neural circuits: the case of leptin action in reproduction. Am J Physiol Regul Integr Comp Physiol 306(1):R1-9. [PubMed: 24196667]  [MGI Ref ID J:208096]

Fujikawa T; Berglund ED; Patel VR; Ramadori G; Vianna CR; Vong L; Thorel F; Chera S; Herrera PL; Lowell BB; Elmquist JK; Baldi P; Coppari R. 2013. Leptin engages a hypothalamic neurocircuitry to permit survival in the absence of insulin. Cell Metab 18(3):431-44. [PubMed: 24011077]  [MGI Ref ID J:203813]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony heterozygous mice may be bred together. Homozygous mice are infertile.
Mating SystemHeterozygote x Heterozygote         (Female x Male)   26-OCT-12
Diet Information LabDiet® 5K20

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $199.90Female or MaleHeterozygous for Leprtm1Jke  
$199.90Female or MaleHomozygous for Leprtm1Jke  
Price per Pair (US dollars $)Pair Genotype
$399.80Heterozygous for Leprtm1Jke x Heterozygous for Leprtm1Jke  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $259.90Female or MaleHeterozygous for Leprtm1Jke  
$259.90Female or MaleHomozygous for Leprtm1Jke  
Price per Pair (US dollars $)Pair Genotype
$519.80Heterozygous for Leprtm1Jke x Heterozygous for Leprtm1Jke  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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