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. Species laboratory mouse Generation N9+1F2+N1p Generation Definitions   Donating Investigator Dr. James Battey, Jr.,   National Institutes of Health

Description
Mice that are homozygous for the targeted mutation are viable, normal in size at birth and do not display any gross physical or behavioral abnormalities. This targeted mutation is X-linked; males bearing the targeted allele display a mutant phenotype. At 15 to 16 weeks of age male mice heterozygous for the mutant allele display increased body weight as compared to wildtype littermates. This mutant mouse strain represents a model that may be useful in studies related to energy metabolism and obesity.

Development
A targeting vector containing neomycin resistance and thymidine kinase genes was used to disrupt exon 2 of the targeted allele. The construct was electroporated into 129X1/SvJ derived Gsi1 embryonic stem (ES) cells. The resulting chimeric animals were backcrossed to C57BL/6 mice.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Brs3^tm1Jfb/Brs3^tm1Jfb

        B6.129X1-Brs3^tm1Jfb

• growth/size phenotype
• increased body weight
  • mutants fed ad lib show significantly greater body weights than wild-type mice fed ad lib starting at 13 weeks of age and continuing throughout the experiment duration; by 32 weeks, mutant animals displayed 28% greater body weight than controls   (MGI Ref ID J:134021)
  • pair-feeding of mutant animals to match caloric intake of ad lib-fed wild-type normalized body weights of mutants so that pair-fed animal weights are similar to ad lib-fed wild-type mice   (MGI Ref ID J:134021)
  • at 10 weeks of age, pair-fed mutants are significantly heavier than wild-type mice   (MGI Ref ID J:134021)
• adipose tissue phenotype
• *normal* adipose tissue phenotype
  • increased weight at 10 weeks of age of pair-fed mutants does not correlate to increased brown adipose tissue compared to wild-type   (MGI Ref ID J:134021)
• • abnormal epididymal fat pad morphology   (MGI Ref ID J:134021)
  • increased brown adipose tissue amount
    • at 36 weeks of age, mutants have significantly more brown fat than wild-type mice   (MGI Ref ID J:134021)
  • increased white adipose tissue amount
    • increased weight at 10 weeks of age of pair-fed mutants is accompanied by significant increases in subcutaneous and epididymal fat   (MGI Ref ID J:134021)
    • at 36 weeks of age, mutants have significantly more subcutaneous and epididymal fat than wild-type mice   (MGI Ref ID J:134021)
• homeostasis/metabolism phenotype
• increased circulating insulin level
  • ad lib-fed mutants show significantly elevated insulin levels relative to ad lib fed wild-type mice   (MGI Ref ID J:134021)
  • pair-fed mutants showed normalized insulin levels to levels in ad lib-fed wild-type mice   (MGI Ref ID J:134021)
• increased circulating leptin level
  • at 10 weeks of age, pair-fed mutants have elevated plasma leptin levels compared to wild-type animals   (MGI Ref ID J:134021)
• behavior/neurological phenotype
• abnormal food intake
  • ad lib-fed mutants show a decrease in grams of food consumed as percentage of body weight compared to wild-type at 20 and 28 weeks of age; less food is consumed relative to body weight   (MGI Ref ID J:134021)
• • increased food intake
    • over course of experiment, mutants fed ad lib show a higher food intake than ad lib-fed wild-type   (MGI Ref ID J:134021)
    • number of food pellets consumed in 24 hours greater in ad lib-fed mutants; number of meals taken in 24 hours is not different from ad lib-fed wild-type mice but meal size is significantly greater   (MGI Ref ID J:134021)

View Research Applications

Research Applications

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

Diabetes and Obesity Research
Hyperinsulinemia
      adult onset
Obesity Without Diabetes

Endocrine Deficiency Research
Hypothalamus/Pituitary Defects

Internal/Organ Research
Gastrointestinal Defects

Metabolism Research
Lipid Metabolism

Neurobiology Research
Behavioral and Learning Defects
Metabolic Defects
Receptor Defects

Research Tools
Neurobiology Research

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Brs3tm1Jfb
Allele Name		targeted mutation 1, James F Battey
Allele Type		Targeted (knock-out)
Common Name(s)		BRS-3 KO;
Mutation Made By		Dr. Lori Hampton,   NIDCD-NIH
Strain of Origin		129X1/SvJ
ES Cell Line Name		GSI-1
ES Cell Line Strain		129X1/SvJ
Gene Symbol and Name		Brs3, bombesin-like receptor 3
Chromosome		X
Gene Common Name(s)		BRS-3;
Molecular Note		Exon 2 has been replaced with a neomycin resistance cassette. No transcript from the disrupted gene was detected in mRNA from brains of homozygous mutant mice by reverse transcription followed by PCR analysis (RT-PCR). [MGI Ref ID J:134021]

Genotyping

Genotyping Information

Genotyping Protocols

Brs3^tm1Jfb, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Ladenheim EE; Hamilton NL; Behles RR; Bi S; Hampton LL; Battey JF; Moran TH. 2008. Factors contributing to obesity in bombesin receptor subtype-3-deficient mice. Endocrinology 149(3):971-8. [PubMed: 18039774]  [MGI Ref ID J:134021]

Additional References

Weber HC; Hampton LL; Jensen RT; Battey JF. 1998. Structure and chromosomal localization of the mouse bombesin receptor subtype 3 gene. Gene 211(1):125-31. [PubMed: 9573346]  [MGI Ref ID J:47585]

Brs3^tm1Jfb related

Guan XM; Chen H; Dobbelaar PH; Dong Y; Fong TM; Gagen K; Gorski J; He S; Howard AD; Jian T; Jiang M; Kan Y; Kelly TM; Kosinski J; Lin LS; Liu J; Marsh DJ; Metzger JM; Miller R; Nargund RP; Palyha O; Shearman L; Shen Z; Stearns R; Strack AM; Stribling S; Tang YS; Wang SP; White A; Yu H; Reitman ML. 2010. Regulation of energy homeostasis by bombesin receptor subtype-3: selective receptor agonists for the treatment of obesity. Cell Metab 11(2):101-12. [PubMed: 20096642]  [MGI Ref ID J:158348]

Xu X; Coats JK; Yang CF; Wang A; Ahmed OM; Alvarado M; Izumi T; Shah NM. 2012. Modular genetic control of sexually dimorphic behaviors. Cell 148(3):596-607. [PubMed: 22304924]  [MGI Ref ID J:181334]

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 & Husbandry	This strain originated on a 129 background, has been backcrossed for 9 generations on the C57BL/6J background. When held in a live colony, breeder pairs were het female X hemi male.
Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

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'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.

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