Strain Name:

B6.129S4-Mc3rtm1Cone/J

Stock Number:

007809

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Availability:

Cryopreserved - Ready for recovery

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Mice homozygous for this targeted mutation exhibit an increase in adiposity without obesity, reduced energy expenditure and can develop salt sensitive hypertension. This mutant mouse strain may be useful in studies of energy homeostasis, regulation of satiety, salt-sensitive hypertension and metabolism.

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; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Additional information on Congenic nomenclature.
Specieslaboratory mouse
Generation?+F1pN1
Generation Definitions
 
Donating Investigator Roger D. Cone,   Vanderbilt University Medical Center

Description
Mice that are homozygous for the targeted mutation are viable and fertile. Female homozygotes at approximately 50 to 60 days of age exhibit significantly heavier body weight when compared to heterozygotes. No gene product (mRNA) is detected by RT-PCR analysis of hypothalamus tissue. Male homozygotes exhibit an approximately 40% increase in body fat at 15-20 weeks of age when compared to wildtype. Heterozygotes display an intermediate increase in body fat percentage of approximately 36%. Although homozygotes have increased adiposity, there is no increased food intake or weight gain and resting basal or total oxygen consumption is lower in mutant mice when compared to wildtype. High fat diet causes an increased respiratory quotient within 24 hours of the diet change. Homozygotes on a low fat diet have a lower respiratory quotient than wildtype. Male homozygotes exhibit an approximately 50% decrease in wheel running behavior. Mutant mice become hypertensive with increased gamma-melanocyte-stimulating hormone plasma levels when placed on high sodium diet. Experimentally induced illness results in enhanced cachexia. This mutant mouse strain may be useful in studies of energy homeostasis, regulation of satiety, salt-sensitive hypertension and metabolism.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt 0.7kb of encoding sequence including the initiation codon. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric animals were crossed to C57BL/6J mice, and then backcrossed to the same for more than 10 generations.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Mc3r
017866   B6(Cg)-Mc3rtm1Butl/J
View Strains carrying other alleles of Mc3r     (1 strain)

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.
Mycobacterium Tuberculosis, Susceptibility to   (MC3R)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Mc3rtm1Cone/Mc3rtm1Cone

        B6.129S4-Mc3rtm1Cone
  • behavior/neurological phenotype
  • decreased compensatory feeding amount
    • after a 16-hour fast, i.p. injection of CCK-8 into females produces a 50% inhibition of food intake in the first 30 minutes in mutants and wild-type and intake continued to be inhibited for up to 180 minutes   (MGI Ref ID J:109494)

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

Mc3rtm1Cone/Mc3r+

        involves: 129S4/SvJae * C57BL/6J
  • growth/size/body phenotype
  • obese
    • heterozygous mice show an intermediate increase in percentage of body fat compared to wild-type (31.8%) and null mice (45.8%) around 15-20 weeks of age   (MGI Ref ID J:78132)

Mc3rtm1Cone/Mc3rtm1Cone

        involves: 129S4/SvJae * C57BL/6J
  • growth/size/body phenotype
  • increased body weight
    • female null mice are significantly heavier than wild-type around 50-60 days of age   (MGI Ref ID J:78132)
    • obese
      • mutants are obese with the proportion of fat increasing by ~40% around 15-20 weeks of age compared to wild-type (31.8% in wild-type vs 45.2% in Mc3r-null mice)   (MGI Ref ID J:78132)
  • increased total body fat amount
    • on a low-fat chow, mutants show increased fat content without gross weight being different   (MGI Ref ID J:78132)
  • homeostasis/metabolism phenotype
  • abnormal respiratory quotient
    • mice show a trend toward greater oxygen consumption on low or high fat diets compared to wild-type   (MGI Ref ID J:78132)
    • when switched to high fat chow, mutants show a dramatic increase in respiratory quotient 24 hours after the switch   (MGI Ref ID J:78132)
    • mutants show a reduced RQ compared to wild-type on a low fat chow diet and a higher RQ on high fat chow   (MGI Ref ID J:78132)
  • behavior/neurological phenotype
  • abnormal food intake
    • despite increased body fat, mice do not exhibit weight gain or increased food consumption   (MGI Ref ID J:78132)
  • adipose tissue phenotype
  • increased total body fat amount
    • on a low-fat chow, mutants show increased fat content without gross weight being different   (MGI Ref ID J:78132)
View Research Applications

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

Cardiovascular Research
Hypertension
      diet-induced
Metabolic Syndrome
Other
      altered fat metabolism

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Mc3rtm1Cone
Allele Name targeted mutation 1, Roger D Cone
Allele Type Targeted (Null/Knockout)
Common Name(s) mc3r-;
Mutation Made By Jonathan Murphy,   Oregon Health & Sciences University
Strain of Origin129S4/SvJae
ES Cell Line NameJ1
ES Cell Line Strain129S4/SvJae
Gene Symbol and Name Mc3r, melanocortin 3 receptor
Chromosome 2
Gene Common Name(s) BMIQ9; MC3; MC3-R; OB20; OQTL;
Molecular Note 0.7kb of sequence was replaced with a neomycin selection cassette at the initiation codon. Homozygous mutant mice were shown to lack transcript via RT-PCR analysis of total hypthalamic RNA. [MGI Ref ID J:78132]

Genotyping

Genotyping Information

Genotyping Protocols

Mc3rtm1Cone, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Butler AA; Kesterson RA; Khong K; Cullen MJ; Pelleymounter MA; Dekoning J; Baetscher M; Cone RD. 2000. A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse. Endocrinology 141(9):3518-21. [PubMed: 10965927]  [MGI Ref ID J:78132]

Additional References

Mc3rtm1Cone related

Almodovar AJ; Luther RJ; Stonebrook CL; Wood PA. 2013. Genomic structure and genetic drift in C57BL/6 congenic metabolic mutant mice. Mol Genet Metab 110(3):396-400. [PubMed: 23867526]  [MGI Ref ID J:205314]

Arteaga-Solis E; Zee T; Emala CW; Vinson C; Wess J; Karsenty G. 2013. Inhibition of leptin regulation of parasympathetic signaling as a cause of extreme body weight-associated asthma. Cell Metab 17(1):35-48. [PubMed: 23312282]  [MGI Ref ID J:195073]

Begriche K; Marston OJ; Rossi J; Burke LK; McDonald P; Heisler LK; Butler AA. 2012. Melanocortin-3 receptors are involved in adaptation to restricted feeding. Genes Brain Behav 11(3):291-302. [PubMed: 22353545]  [MGI Ref ID J:198040]

Butler AA; Marks DL; Fan W; Kuhn CM; Bartolome M; Cone RD. 2001. Melanocortin-4 receptor is required for acute homeostatic responses to increased dietary fat. Nat Neurosci 4(6):605-11. [PubMed: 11369941]  [MGI Ref ID J:69814]

Fan W; Ellacott KL; Halatchev IG; Takahashi K; Yu P; Cone RD. 2004. Cholecystokinin-mediated suppression of feeding involves the brainstem melanocortin system. Nat Neurosci 7(4):335-6. [PubMed: 15034587]  [MGI Ref ID J:109494]

Kumar KG; Trevaskis JL; Lam DD; Sutton GM; Koza RA; Chouljenko VN; Kousoulas KG; Rogers PM; Kesterson RA; Thearle M; Ferrante AW Jr; Mynatt RL; Burris TP; Dong JZ; Halem HA; Culler MD; Heisler LK; Stephens JM; Butler AA. 2008. Identification of adropin as a secreted factor linking dietary macronutrient intake with energy homeostasis and lipid metabolism. Cell Metab 8(6):468-81. [PubMed: 19041763]  [MGI Ref ID J:144378]

Lippert RN; Ellacott KL; Cone RD. 2014. Gender-specific roles for the melanocortin-3 receptor in the regulation of the mesolimbic dopamine system in mice. Endocrinology 155(5):1718-27. [PubMed: 24605830]  [MGI Ref ID J:210728]

Marks DL; Butler AA; Turner R; Brookhart G; Cone RD. 2003. Differential role of melanocortin receptor subtypes in cachexia. Endocrinology 144(4):1513-23. [PubMed: 12639936]  [MGI Ref ID J:115698]

Ni XP; Pearce D; Butler AA; Cone RD; Humphreys MH. 2003. Genetic disruption of gamma-melanocyte-stimulating hormone signaling leads to salt-sensitive hypertension in the mouse. J Clin Invest 111(8):1251-8. [PubMed: 12697744]  [MGI Ref ID J:82967]

Nogueiras R; Wiedmer P; Perez-Tilve D; Veyrat-Durebex C; Keogh JM; Sutton GM; Pfluger PT; Castaneda TR; Neschen S; Hofmann SM; Howles PN; Morgan DA; Benoit SC; Szanto I; Schrott B; Schurmann A; Joost HG; Hammond C; Hui DY; Woods SC; Rahmouni K; Butler AA; Farooqi IS; O'Rahilly S; Rohner-Jeanrenaud F; Tschop MH. 2007. The central melanocortin system directly controls peripheral lipid metabolism. J Clin Invest 117(11):3475-88. [PubMed: 17885689]  [MGI Ref ID J:127528]

Perez-Tilve D; Hofmann SM; Basford J; Nogueiras R; Pfluger PT; Patterson JT; Grant E; Wilson-Perez HE; Granholm NA; Arnold M; Trevaskis JL; Butler AA; Davidson WS; Woods SC; Benoit SC; Sleeman MW; DiMarchi RD; Hui DY; Tschop MH. 2010. Melanocortin signaling in the CNS directly regulates circulating cholesterol. Nat Neurosci 13(7):877-82. [PubMed: 20526334]  [MGI Ref ID J:161611]

Renquist BJ; Murphy JG; Larson EA; Olsen D; Klein RF; Ellacott KL; Cone RD. 2012. Melanocortin-3 receptor regulates the normal fasting response. Proc Natl Acad Sci U S A 109(23):E1489-98. [PubMed: 22573815]  [MGI Ref ID J:184765]

Sutton GM; Perez-Tilve D; Nogueiras R; Fang J; Kim JK; Cone RD; Gimble JM; Tschop MH; Butler AA. 2008. The melanocortin-3 receptor is required for entrainment to meal intake. J Neurosci 28(48):12946-55. [PubMed: 19036988]  [MGI Ref ID J:142498]

Sutton GM; Trevaskis JL; Hulver MW; McMillan RP; Markward NJ; Babin MJ; Meyer EA; Butler AA. 2006. Diet-genotype interactions in the development of the obese, insulin-resistant phenotype of C57BL/6J mice lacking melanocortin-3 or -4 receptors. Endocrinology 147(5):2183-96. [PubMed: 16469808]  [MGI Ref ID J:128237]

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, these mice can be bred as homozygotes.

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* $2140.00
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 willfulfill 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 10 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* $2782.00
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 willfulfill 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 10 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
   000664 C57BL/6J
 
  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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