Strain Name:

B6.129-Leprtm1Mgmj/J

Stock Number:

008518

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Mice homozygous for the LeprS1138 mutant allele (or s/s mice) have a Tyr->Ser replacement at amino acid residue 1138 of the leptin receptor long form (LRb)-specific exon 18b that specifically disrupts LRb-STAT3 transcription factor signaling, and may be useful for studying LRb-STAT3 signaling in the physiological and metabolic function of leptin; specifically body energy homeostasis and neuroendocrine function, glucose homeostasis, melanocortin production, neuropeptide Y, obesity, diabetes, fertility and growth.

Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Congenic; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
 
Donating Investigator Martin G Myers,   University of Michigan Medical School

Description
Mice homozygous for the LeprS1138 mutant allele (or s/s mice) are viable and partially fertile with a Tyr->Ser replacement at amino acid residue 1138 of the leptin receptor long form (LRb)-specific exon 18b. The mutation specifically disrupts LRb-STAT3 transcription factor signaling. The mutant protein, LRbS1138, is expressed normally on the cell surface and mediates other leptin signals normally, but fails to activate STAT3. Similar to homozygous db/db mice (which are devoid of all leptin signaling), homozygous s/s mice display hyperphagia, decreased energy expenditure, and decreased thyroid function resulting in profound obesity and dramatically increased serum leptin levels compared to wild-type. Unlike db/db mice, however, s/s mice are fertile and long bodied, have improved glucose tolerance (less hyperglycemic), are not protected from intimal hyperplasia following vessel injury, and do not exhibit elevated hypothalamic expression of neuropeptide Y (NPY). Homozygous LeprS1138 mutant mice may be useful for studying LRb-STAT3 signaling in the physiological and metabolic function of leptin; specifically body energy homeostasis and neuroendocrine function, glucose homeostasis, melanocortin production, neuropeptide Y, obesity, diabetes, fertility and growth.

Development
A targeting vector was designed to replace the tyrosine residue at amino acid 1138 of the leptin receptor long form (LRb)-specific exon 18b of the targeted gene with a serine residue (and also insert a neo cassette downstream of exon 18b). The donating investigator reports that the construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells and the resulting chimeric animals were bred with C57BL/6 (Taconic) mice to generate LRbS1138 mutant mice. These mice were then backcrossed at least 15 generations to C57BL/6 (Taconic) prior to arrival at The Jackson Laboratory. Upon arrival, mutant mice were bred with C57BL/6NJ (Stock No. 005304) for at least one generation to establish the colony.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J (approximate)
   005304 C57BL/6NJ (approximate)
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying other alleles of Lepr     (18 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Model with phenotypic similarity to human disease where etiologies are distinct. Human genes are associated with this disease. Orthologs of these genes do not appear in the mouse genotype(s).
Obesity
- 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

Leprtm1Mgmj/Lepr+

        B6.129-Leprtm1Mgmj
  • growth/size phenotype
  • increased body weight
    • slight but significant increase in body weight compared to wild-type mice   (MGI Ref ID J:82334)

Leprtm1Mgmj/Leprtm1Mgmj

        B6.129-Leprtm1Mgmj
  • growth/size phenotype
  • increased body length
    • snout to anus length is increased by about 5% compared to wild-type mice   (MGI Ref ID J:82334)
  • obese
    • body weight is 2- to 3-fold more than in wild-type mice by 10 weeks of age   (MGI Ref ID J:82334)
    • however, body weight is 10% and 20% less in males and females, respectively, compared to Leprrdb homozygotes   (MGI Ref ID J:82334)
  • behavior/neurological phenotype
  • polyphagia   (MGI Ref ID J:82334)
  • homeostasis/metabolism phenotype
  • abnormal energy expenditure
    • mice pair-fed with wild-type mice gain more weight and adipose tissue than wild-type mice   (MGI Ref ID J:82334)
  • abnormal glucose homeostasis   (MGI Ref ID J:82334)
    • increased circulating glucose level
      • increase in glucose is less than in Leprrdb homozygotes   (MGI Ref ID J:82334)
    • increased circulating insulin level   (MGI Ref ID J:82334)
  • abnormal vascular wound healing
    • increased neointimal hyperplasia relative to Leprdb 4 weeks after femoral artery injury   (MGI Ref ID J:135034)
  • increased circulating leptin level   (MGI Ref ID J:82334)
  • increased circulating triglyceride level   (MGI Ref ID J:82334)
  • reproductive system phenotype
  • delayed estrous cycle
    • slight delay in the onset of oestrous cycling, median onset at 42 days rather than 36 days as in wild-type mice   (MGI Ref ID J:82334)
    • however, all females show signs of vaginal oestrous and no defects in ovulation are seen   (MGI Ref ID J:82334)
  • reduced female fertility
    • only about 40% of females are fertile   (MGI Ref ID J:82334)
  • endocrine/exocrine gland phenotype
  • abnormal lactation
    • pups born to homozygous females die within 24 h without milk in their stomachs unless fostered to wild-type mothers   (MGI Ref ID J:82334)
  • cardiovascular system phenotype
  • abnormal vascular wound healing
    • increased neointimal hyperplasia relative to Leprdb 4 weeks after femoral artery injury   (MGI Ref ID J:135034)
  • decreased systemic arterial blood pressure
    • similar to to Leprdb   (MGI Ref ID J:135034)
  • integument phenotype
  • abnormal lactation
    • pups born to homozygous females die within 24 h without milk in their stomachs unless fostered to wild-type mothers   (MGI Ref ID J:82334)

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Leprtm1Mgmj/Leprtm1Mgmj

        involves: 129/Sv
  • reproductive system phenotype
  • absent estrus
    • in 5 of 8 mice   (MGI Ref ID J:164339)
  • female infertility
View Research Applications

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

Cardiovascular Research
Other
      altered fat metabolism
      altered lipoprotein profile

Cell Biology Research
Signal Transduction
Transcriptional Regulation

Diabetes and Obesity Research
Impaired Insulin Processing
Impaired Wound Healing
Obesity With Diabetes
Obesity Without Diabetes

Metabolism Research
Lipid Metabolism

Neurobiology Research
Metabolic Defects

Research Tools
Cardiovascular Research
Diabetes and Obesity Research
Metabolism Research
Neurobiology Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Leprtm1Mgmj
Allele Name targeted mutation 1, Martin G Myers, Jr
Allele Type Targeted (knock-in)
Common Name(s) leprS1138; leprs; s;
Mutation Made By Martin Myers,   University of Michigan Medical School
Strain of Origin129/Sv
Promoter Lepr, leptin receptor, mouse, laboratory
Molecular Note Tyrosine 1138 of exon 18b was replaced with a serine residue (Y1138S) and a neomycin resistance cassette was inserted into the downstream intron via homologous recombination. The Y1138S amino acid substitution specifically disrupts the leptin receptor long form (LRb)-STAT3 signal. Expression of the knock-in allele in mutant animals was confirmed by semi-quantitative RT-PCR analysis of hypothalamus RNA. [MGI Ref ID J:82334]

Genotyping

Genotyping Information

Genotyping Protocols

Leprtm1Mgmj, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Bates SH; Stearns WH; Dundon TA; Schubert M; Tso AW; Wang Y; Banks AS; Lavery HJ; Haq AK; Maratos-Flier E; Neel BG; Schwartz MW; Myers MG Jr. 2003. STAT3 signalling is required for leptin regulation of energy balance but not reproduction. Nature 421(6925):856-9. [PubMed: 12594516]  [MGI Ref ID J:82334]

Leinninger GM; Myers MG Jr. 2008. LRb signals act within a distributed network of leptin-responsive neurones to mediate leptin action. Acta Physiol (Oxf) 192(1):49-59. [PubMed: 18171429]  [MGI Ref ID J:137518]

Additional References

Leprtm1Mgmj related

Bates SH; Dundon TA; Seifert M; Carlson M; Maratos-Flier E; Myers MG Jr. 2004. LRb-STAT3 signaling is required for the neuroendocrine regulation of energy expenditure by leptin. Diabetes 53(12):3067-73. [PubMed: 15561935]  [MGI Ref ID J:94585]

Bates SH; Kulkarni RN; Seifert M; Myers MG Jr. 2005. Roles for leptin receptor/STAT3-dependent and -independent signals in the regulation of glucose homeostasis. Cell Metab 1(3):169-78. [PubMed: 16054060]  [MGI Ref ID J:129847]

Bodary PF; Shen Y; Ohman M; Bahrou KL; Vargas FB; Cudney SS; Wickenheiser KJ; Myers MG Jr; Eitzman DT. 2007. Leptin regulates neointima formation after arterial injury through mechanisms independent of blood pressure and the leptin receptor/STAT3 signaling pathways involved in energy balance. Arterioscler Thromb Vasc Biol 27(1):70-6. [PubMed: 17095713]  [MGI Ref ID J:135034]

Bouret SG; Bates SH; Chen S; Myers MG Jr; Simerly RB. 2012. Distinct roles for specific leptin receptor signals in the development of hypothalamic feeding circuits. J Neurosci 32(4):1244-52. [PubMed: 22279209]  [MGI Ref ID J:180585]

Buettner C; Muse ED; Cheng A; Chen L; Scherer T; Pocai A; Su K; Cheng B; Li X; Harvey-White J; Schwartz GJ; Kunos G; Rossetti L; Buettner C. 2008. Leptin controls adipose tissue lipogenesis via central, STAT3-independent mechanisms. Nat Med 14(6):667-75. [PubMed: 18516053]  [MGI Ref ID J:137042]

Buettner C; Pocai A; Muse ED; Etgen AM; Myers MG Jr; Rossetti L. 2006. Critical role of STAT3 in leptin's metabolic actions. Cell Metab 4(1):49-60. [PubMed: 16814732]  [MGI Ref ID J:129709]

Gerin I; Louis GW; Zhang X; Prestwich TC; Kumar TR; Myers MG Jr; Macdougald OA; Nothnick WB. 2009. Hyperphagia and obesity in female mice lacking tissue inhibitor of metalloproteinase-1. Endocrinology 150(4):1697-704. [PubMed: 19036876]  [MGI Ref ID J:158084]

Gove ME; Rhodes DH; Pini M; van Baal JW; Sennello JA; Fayad R; Cabay RJ; Myers MG Jr; Fantuzzi G. 2009. Role of leptin receptor-induced STAT3 signaling in modulation of intestinal and hepatic inflammation in mice. J Leukoc Biol 85(3):491-6. [PubMed: 19052144]  [MGI Ref ID J:146076]

Mancuso P; Peters-Golden M; Goel D; Goldberg J; Brock TG; Greenwald-Yarnell M; Myers MG Jr. 2011. Disruption of leptin receptor-STAT3 signaling enhances leukotriene production and pulmonary host defense against pneumococcal pneumonia. J Immunol 186(2):1081-90. [PubMed: 21148797]  [MGI Ref ID J:168784]

Munzberg H; Jobst EE; Bates SH; Jones J; Villanueva E; Leshan R; Bjornholm M; Elmquist J; Sleeman M; Cowley MA; Myers MG Jr. 2007. Appropriate inhibition of orexigenic hypothalamic arcuate nucleus neurons independently of leptin receptor/STAT3 signaling. J Neurosci 27(1):69-74. [PubMed: 17202473]  [MGI Ref ID J:117213]

Robertson S; Ishida-Takahashi R; Tawara I; Hu J; Patterson CM; Jones JC; Kulkarni RN; Myers MG Jr. 2010. Insufficiency of Janus kinase 2-autonomous leptin receptor signals for most physiologic leptin actions. Diabetes 59(4):782-90. [PubMed: 20068132]  [MGI Ref ID J:164339]

Saadat N; Iglayreger HB; Myers MG Jr; Bodary P; Gupta SV. 2012. Differences in metabolomic profiles of male db/db and s/s, leptin receptor mutant mice. Physiol Genomics 44(6):374-81. [PubMed: 22318992]  [MGI Ref ID J:182608]

Thorn SR; Giesy SL; Myers MG Jr; Boisclair YR. 2010. Mammary ductal growth is impaired in mice lacking leptin-dependent signal transducer and activator of transcription 3 signaling. Endocrinology 151(8):3985-95. [PubMed: 20501669]  [MGI Ref ID J:169507]

Villanueva EC; Munzberg H; Cota D; Leshan RL; Kopp K; Ishida-Takahashi R; Jones JC; Fingar DC; Seeley RJ; Myers MG Jr. 2009. Complex regulation of mammalian target of rapamycin complex 1 in the basomedial hypothalamus by leptin and nutritional status. Endocrinology 150(10):4541-51. [PubMed: 19628573]  [MGI Ref ID J:157328]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, heterozygous mice may be bred together. The donating investigator reports that homozygous mice are partially fertile.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


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

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2250.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2925.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.
    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
    Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J (approximate)
   005304 C57BL/6NJ (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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