Strain Name:

FVB/N-Adrb3tm1Lowl/J

Stock Number:

006402

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Availability:

Cryopreserved - Ready for recovery

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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 Coisogenic; Mutant Strain; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Specieslaboratory mouse
Generation?+F1pN1
Generation Definitions
 
Donating Investigator Bradford B. Lowell,   Beth Israel Deaconess Med Cntr (Harvard)

Description
Homozygous mice are viable and fertile. No gene product (mRNA) is detected by Northern blot analysis from homozygous brown or white adipose tissue. Homozygous mice have modest increases in fat stores (female more than male). In contrast to control animals, homozygous mice are unresponsive to beta-3 adrenergic receptor (beta3-AR) agonist treatment (no effect on adenylate cyclase activity, lipolysis, or gastro-intestinal motility). These mutant mice may be useful in studies of energy balance, obesity, fat metabolism, cholesterol homeostasis, diabetes, and pharmacological screening of beta3-AR agonists for potential drug treatment.

Development
A targeting vector was designed to replace the portion of the endogenous gene coding for residue 120-222 with a PGK-neo cassette. The construct was injected into FVB/N zygotes and these were transferred into FVB/N pseudopregnant females. Offspring heterozygous for the targeted mutation (founder line B2) were maintained on the FVB/N genetic background and then bred together to create a homozygous colony.

Control Information

  Control
   001800 FVB/NJ
 
  Considerations for Choosing Controls

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.
Obesity   (ADRB3)
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.

Adrb3tm1Lowl/Adrb3tm1Lowl

        FVB/N-Adrb3tm1Lowl
  • adipose tissue phenotype
  • increased parametrial fat pad weight
    • parametrial fat pads weigh 99% more than in controls   (MGI Ref ID J:30060)
  • increased total body fat amount
    • body fat stores are increased by 34% in males, however epididymal fat pads weights are normal   (MGI Ref ID J:30060)
    • body fat stores are increased by 131% in females   (MGI Ref ID J:30060)
  • homeostasis/metabolism phenotype
  • abnormal physiological response to xenobiotic
    • mutants exhibit complete loss of beta3-adrenergic receptor agonist (CL 316,243)-induced stimulation of adenylate cyclase activity, lipolysis, increase of CO2 consumption, serum FFA levels, plasma insulin levels, and reduction of blood glucose levels and food intake   (MGI Ref ID J:30060)
    • absence of isoproterenol-stimulated lipolysis in adipocytes in the presence of PIA, an A1 adenosine receptor agonist   (MGI Ref ID J:30060)
  • growth/size/body phenotype
  • increased total body fat amount
    • body fat stores are increased by 34% in males, however epididymal fat pads weights are normal   (MGI Ref ID J:30060)
    • body fat stores are increased by 131% in females   (MGI Ref ID J:30060)
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

Metabolism Research
Lipid Metabolism

Research Tools
Cardiovascular Research
Diabetes and Obesity Research
Metabolism Research

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Adrb3tm1Lowl
Allele Name targeted mutation 1, Bradford B Lowell
Allele Type Targeted (Null/Knockout)
Common Name(s) beta3-AR -;
Mutation Made By Bradford Lowell,   Beth Israel Deaconess Med Cntr (Harvard)
Strain of OriginFVB/N
ES Cell Line NameOther (see notes)
Gene Symbol and Name Adrb3, adrenergic receptor, beta 3
Chromosome 8
Gene Common Name(s) ADRB; Adrb-3; BETA3AR; Beta-3 AR; Beta-3 adrenoceptor; beta 3-AR; beta3-adrenergic receptor;
General Note This allele was generated by direct injection of DNA vectors into FVB/N zygotes. (J:30060)
Molecular Note A 306bp genomic fragment containing the sequences encoding the third through the fifth transmembrane domains was replaced with a neomycin selection cassette. An RNase protection assay demonstrated that the encoded transcript was not detectable in brown adipose tissue of homozygous mice. [MGI Ref ID J:30060]

Genotyping

Genotyping Information

Genotyping Protocols

Adrb3tm1Lowl, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Susulic VS; Frederich RC; Lawitts J; Tozzo E; Kahn BB; Harper ME; Himms-Hagen J; Flier JS; Lowell BB. 1995. Targeted disruption of the beta 3-adrenergic receptor gene. J Biol Chem 270(49):29483-92. [PubMed: 7493988]  [MGI Ref ID J:30060]

Additional References

Adrb3tm1Lowl related

Angers M; Uldry M; Kong D; Gimble JM; Jetten AM. 2008. Mfsd2a encodes a novel major facilitator superfamily domain-containing protein highly induced in brown adipose tissue during fasting and adaptive thermogenesis. Biochem J 416(3):347-55. [PubMed: 18694395]  [MGI Ref ID J:143949]

Bachman ES; Dhillon H; Zhang CY; Cinti S; Bianco AC; Kobilka BK; Lowell BB. 2002. betaAR signaling required for diet-induced thermogenesis and obesity resistance. Science 297(5582):843-5. [PubMed: 12161655]  [MGI Ref ID J:79309]

Boss O; Bachman E; Vidal-Puig A; Zhang CY; Peroni O; Lowell BB. 1999. Role of the beta(3)-adrenergic receptor and/or a putative beta(4)-adrenergic receptor on the expression of uncoupling proteins and peroxisome proliferator-activated receptor-gamma coactivator-1. Biochem Biophys Res Commun 261(3):870-6. [PubMed: 10441518]  [MGI Ref ID J:56769]

Boucher J; Castan-Laurell I; Le Lay S; Grujic D; Sibrac D; Krief S; Lafontan M; Lowell BB; Dugail I; Saulnier-Blache JS; Valet P. 2002. Human alpha 2A-adrenergic receptor gene expressed in transgenic mouse adipose tissue under the control of its regulatory elements. J Mol Endocrinol 29(2):251-64. [PubMed: 12370125]  [MGI Ref ID J:134116]

Calvert JW; Condit ME; Aragon JP; Nicholson CK; Moody BF; Hood RL; Sindler AL; Gundewar S; Seals DR; Barouch LA; Lefer DJ. 2011. Exercise protects against myocardial ischemia-reperfusion injury via stimulation of beta(3)-adrenergic receptors and increased nitric oxide signaling: role of nitrite and nitrosothiols. Circ Res 108(12):1448-58. [PubMed: 21527738]  [MGI Ref ID J:185691]

Chernogubova E; Hutchinson DS; Nedergaard J; Bengtsson T. 2005. Alpha1- and beta1-adrenoceptor signaling fully compensates for beta3-adrenoceptor deficiency in brown adipocyte norepinephrine-stimulated glucose uptake. Endocrinology 146(5):2271-84. [PubMed: 15665039]  [MGI Ref ID J:109477]

Chow A; Lucas D; Hidalgo A; Mendez-Ferrer S; Hashimoto D; Scheiermann C; Battista M; Leboeuf M; Prophete C; van Rooijen N; Tanaka M; Merad M; Frenette PS. 2011. Bone marrow CD169+ macrophages promote the retention of hematopoietic stem and progenitor cells in the mesenchymal stem cell niche. J Exp Med 208(2):261-71. [PubMed: 21282381]  [MGI Ref ID J:176846]

Claustre Y; Leonetti M; Santucci V; Bougault I; Desvignes C; Rouquier L; Aubin N; Keane P; Busch S; Chen Y; Palejwala V; Tocci M; Yamdagni P; Didier M; Avenet P; Le Fur G; Oury-Donat F; Scatton B; Steinberg R. 2008. Effects of the beta3-adrenoceptor (Adrb3) agonist SR58611A (amibegron) on serotonergic and noradrenergic transmission in the rodent: relevance to its antidepressant/anxiolytic-like profile. Neuroscience 156(2):353-64. [PubMed: 18691638]  [MGI Ref ID J:140856]

Cohen ML; Bloomquist W; Ito M; Lowell BB. 2000. Beta3 receptors mediate relaxation in stomach fundus whereas a fourth beta receptor mediates tachycardia in atria from transgenic beta3 receptor knockout mice Receptors Channels 7(1):17-23. [PubMed: 10800773]  [MGI Ref ID J:62444]

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]

Heffernan M; Summers RJ; Thorburn A; Ogru E; Gianello R; Jiang WJ; Ng FM. 2001. The effects of human GH and its lipolytic fragment (AOD9604) on lipid metabolism following chronic treatment in obese mice and beta(3)-AR knock-out mice. Endocrinology 142(12):5182-9. [PubMed: 11713213]  [MGI Ref ID J:115409]

Hutchinson DS; Chernogubova E; Dallner OS; Cannon B; Bengtsson T. 2005. Beta-adrenoceptors, but not alpha-adrenoceptors, stimulate AMP-activated protein kinase in brown adipocytes independently of uncoupling protein-1. Diabetologia 48(11):2386-95. [PubMed: 16160864]  [MGI Ref ID J:104710]

Ito M; Grujic D; Abel ED; Vidal-Puig A; Susulic VS; Lawitts J; Harper ME; Himms-Hagen J; Strosberg AD; Lowell BB. 1998. Mice expressing human but not murine beta3-adrenergic receptors under the control of human gene regulatory elements. Diabetes 47(9):1464-71. [PubMed: 9726236]  [MGI Ref ID J:49477]

Ke Y; Qiu J; Ogus S; Shen WJ; Kraemer FB; Chehab FF. 2003. Overexpression of leptin in transgenic mice leads to decreased basal lipolysis, PKA activity, and perilipin levels. Biochem Biophys Res Commun 312(4):1165-70. [PubMed: 14651995]  [MGI Ref ID J:94674]

Lay SL; Boucher J; Rey A; Castan-Laurell I; Krief S; Ferre P; Valet P; Dugail I. 2001. Decreased resistin expression in mice with different sensitivities to a high-fat diet. Biochem Biophys Res Commun 289(2):564-7. [PubMed: 11716511]  [MGI Ref ID J:73107]

Mantzoros CS; Qu D; Frederich RC; Susulic VS; Lowell BB; Maratos-Flier E; Flier JS. 1996. Activation of beta(3) adrenergic receptors suppresses leptin expression and mediates a leptin-independent inhibition of food intake in mice. Diabetes 45(7):909-14. [PubMed: 8666142]  [MGI Ref ID J:33689]

Mattsson CL; Csikasz RI; Chernogubova E; Yamamoto DL; Hogberg HT; Amri EZ; Hutchinson DS; Bengtsson T. 2011. beta-Adrenergic receptors increase UCP1 in human MADS brown adipocytes and rescue cold-acclimated beta-adrenergic receptor-knockout mice via nonshivering thermogenesis. Am J Physiol Endocrinol Metab 301(6):E1108-18. [PubMed: 21878665]  [MGI Ref ID J:182167]

Mendez-Ferrer S; Lucas D; Battista M; Frenette PS. 2008. Haematopoietic stem cell release is regulated by circadian oscillations. Nature 452(7186):442-7. [PubMed: 18256599]  [MGI Ref ID J:134224]

Miura S; Kawanaka K; Kai Y; Tamura M; Goto M; Shiuchi T; Minokoshi Y; Ezaki O. 2007. An increase in murine skeletal muscle peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) mRNA in response to exercise is mediated by beta-adrenergic receptor activation. Endocrinology 148(7):3441-8. [PubMed: 17446185]  [MGI Ref ID J:129633]

Moens AL; Leyton-Mange JS; Niu X; Yang R; Cingolani O; Arkenbout EK; Champion HC; Bedja D; Gabrielson KL; Chen J; Xia Y; Hale AB; Channon KM; Halushka MK; Barker N; Wuyts FL; Kaminski PM; Wolin MS; Kass DA; Barouch LA. 2009. Adverse ventricular remodeling and exacerbated NOS uncoupling from pressure-overload in mice lacking the beta3-adrenoreceptor. J Mol Cell Cardiol 47(5):576-85. [PubMed: 19766235]  [MGI Ref ID J:155006]

Pulinilkunnil T; He H; Kong D; Asakura K; Peroni OD; Lee A; Kahn BB. 2011. Adrenergic Regulation of AMP-activated Protein Kinase in Brown Adipose Tissue in Vivo. J Biol Chem 286(11):8798-809. [PubMed: 21209093]  [MGI Ref ID J:170535]

Scheiermann C; Kunisaki Y; Lucas D; Chow A; Jang JE; Zhang D; Hashimoto D; Merad M; Frenette PS. 2012. Adrenergic nerves govern circadian leukocyte recruitment to tissues. Immunity 37(2):290-301. [PubMed: 22863835]  [MGI Ref ID J:187383]

Schutsky K; Ouyang M; Castelino CB; Zhang L; Thomas SA. 2011. Stress and Glucocorticoids Impair Memory Retrieval via {beta}2-Adrenergic, Gi/o-Coupled Suppression of cAMP Signaling. J Neurosci 31(40):14172-81. [PubMed: 21976502]  [MGI Ref ID J:177184]

Stemmelin J; Cohen C; Yalcin I; Keane P; Griebel G. 2010. Implication of beta3-adrenoceptors in the antidepressant-like effects of amibegron using Adrb3 knockout mice in the chronic mild stress. Behav Brain Res 206(2):310-2. [PubMed: 19744528]  [MGI Ref ID J:153973]

Swoap SJ; Li C; Wess J; Parsons AD; Williams TD; Overton JM. 2008. Vagal tone dominates autonomic control of mouse heart rate at thermoneutrality. Am J Physiol Heart Circ Physiol 294(4):H1581-8. [PubMed: 18245567]  [MGI Ref ID J:135270]

Valet P; Grujic D; Wade J; Ito M; Zingaretti MC; Soloveva V; Ross SR; Graves RA; Cinti S; Lafontan M; Lowell BB. 2000. Expression of human alpha 2-adrenergic receptors in adipose tissue of beta 3-adrenergic receptor-deficient mice promotes diet-induced obesity J Biol Chem 275(44):34797-802. [PubMed: 10948198]  [MGI Ref ID J:65476]

Varghese P; Harrison RW; Lofthouse RA; Georgakopoulos D; Berkowitz DE; Hare JM. 2000. beta(3)-adrenoceptor deficiency blocks nitric oxide-dependent inhibition of myocardial contractility. J Clin Invest 106(5):697-703. [PubMed: 10974023]  [MGI Ref ID J:64547]

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, homozygous mice are bred together.

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 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 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 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 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
   001800 FVB/NJ
 
  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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