Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote         (Female x Male) Species laboratory mouse Generation N7+F1 (08-MAY-08)   Donating Investigator Roger Cone,   Vollum Institute

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

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Mc3r^tm1Cone/Mc3r^tm1Cone

        B6.129S4-Mc3r^tm1Cone

• behavior/neurological phenotype
• decreased eating behavior (MGI Ref ID J:109494)
  • 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

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

Mc3r^tm1Cone/Mc3r⁺

        involves: 129S4/SvJae * C57BL/6J

• growth/size phenotype
• obese (MGI Ref ID J:78132)
  • 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

Mc3r^tm1Cone/Mc3r^tm1Cone

        involves: 129S4/SvJae * C57BL/6J

• growth/size phenotype
• increased body weight (MGI Ref ID J:78132)
  • female null mice are significantly heavier than wild-type around 50-60 days of age
• obese (MGI Ref ID J:78132)
  • 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)
• homeostasis/metabolism phenotype
• abnormal respiratory quotient (MGI Ref ID J:78132)
  • mice show a trend toward greater oxygen consumption on low or high fat diets compared to wild-type
  • when switched to high fat chow, mutants show a dramatic increase in respiratory quotient 24 hours after the switch
  • mutants show a reduced RQ compared to wild-type on a low fat chow diet and a higher RQ on high fat chow
• behavior/neurological phenotype
• abnormal food intake (MGI Ref ID J:78132)
  • despite increased body fat, mice do not exhibit weight gain or increased food consumption
• adipose tissue phenotype
• increased adipose tissue amount (MGI Ref ID J:78132)
  • on a low-fat chow, mutants show increased fat content without gross weight being different

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

Allele Symbol		Mc3rtm1Cone
Allele Name		targeted mutation 1, Roger D Cone
Allele Type		Targeted (knock-out)
Common Name(s)		mc3r-/-;
Mutation Made By		Jonathan Murphy,   Oregon Health & Sciences University
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Mc3r, melanocortin 3 receptor
Chromosome		2
Gene Common Name(s)		MC3; MC3-R;
Molecular Note		0.7kb of sequence was deleted by the insertion of 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

Mc3r^tm1Cone, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

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

Mc3r^tm1Cone related

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]

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]

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

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX12

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice can be bred as homozygotes.
Mating System	Homozygote x Homozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

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.

---

Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.