Strain Name:

B6.129-Adrbk1tm1Mca/J

Stock Number:

012430

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Cryopreserved - Ready for recovery

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This Adrbk1 (adrenergic receptor kinase, beta 1; also known as Grk2) targeted mutation strain may be useful for delineating the role of GRK2 activity in developmental processes. Homozygotes show defects which include failure of the heart to develop properly (thin myocardium syndrome) leading to embryonic lethality. Heterozygotes exhibit altered adrenergic receptor-regulated heart function as adults.

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
 
Donating Investigator Robert Lefkowitz,   Duke University Medical Center

Description
Adrbk1 (adrenergic receptor kinase, beta 1; also known as Grk2) is the main G-protein-coupled receptor kinase in developing embryos, and lack of GRK2 expression results in embryonic lethality before gestational day 15.5. Homozygotes with this targeted mutation show defects which include failure of the heart to develop properly (thin myocardium syndrome). This strain will be useful for delineating the role of GRK2 activity in developmental processes. Heterozygotes exhibit altered adrenergic receptor-regulated heart function when tested as adults, and these mice can be useful for exploring the role of GRK2 function in the regulation of any G-protein coupled receptor subtype. Homozygous embryos lack GRK2 immunoreactivity. Heterozygote mouse brain and heart have 50% of normal GRK2 immunoreactivity.

Development
Exons 5-8 were replaced with a PGK-neomycin resistance cassette (in the anti-sense orientation) using 129-derived embryonic stem (ES) cells. Exon 8 encodes the consensus catalytic subdomain I of the protein kinase. This line was backcrossed to C57BL/6 for more than ten generations by the donating laboratory.

Control Information

  Control
   Wild-type from the colony
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Adrbk1
012458   STOCK Adrbk1tm1Gwd/J
View Strains carrying other alleles of Adrbk1     (1 strain)

Phenotype

Phenotype Information

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.

Adrbk1tm1Mca/Adrbk1tm1Mca

        involves: 129
  • mortality/aging
  • complete lethality throughout fetal growth and development
    • no homozygotes survive beyond E15.5 as a result of heart failure   (MGI Ref ID J:36567)
  • partial embryonic lethality during organogenesis
    • starting at E9, homozygotes exhibit a progressive decline in embryonic survival up to E15.5   (MGI Ref ID J:36567)
  • cardiovascular system phenotype
  • abnormal interventricular septum morphology
    • at E12.5-E15.5, homozygotes display hypoplasia and dysplasia of the interventricular septum, with persistence of an aberrantly wide interventricular foramen   (MGI Ref ID J:36567)
  • abnormal myocardial trabeculae morphology
    • at E12.5-E15.5, homozygotes display abnormally thinned trabeculae in the ventricles and atria   (MGI Ref ID J:36567)
    • trabecula carnea hypoplasia
      • at E12.5-E15.5, homozygotes show disorganized trabeculae in the ventricular wall   (MGI Ref ID J:36567)
  • atrium hypoplasia
    • at E12.5-E15.5, homozygotes display hypoplasia of the right and left atria   (MGI Ref ID J:36567)
  • decreased ventricle muscle contractility
    • at E12.5-E13.5, homozygotes display a >70% decrease in left ventricular ejection fraction, indicating ventricular chamber dysfunction   (MGI Ref ID J:36567)
  • dilated heart right atrium
    • at E13, homozygotes display a dilated right atrium   (MGI Ref ID J:36567)
  • disorganized myocardium
    • at E12.5-E15.5, homozygotes exhibit absence of organization or differentiation of the ventricular myocardium   (MGI Ref ID J:36567)
  • heart hypoplasia
    • at E12.5-E15.5, homozygotes display hypoplasia and dysplasia of the myocardium   (MGI Ref ID J:36567)
    • mutant ventricular and atrial cavities (lumina) appear unusually large as a result of hypoplasia   (MGI Ref ID J:36567)
  • thin myocardium compact layer
    • at E12.5-E15.5, homozygotes display an abnormally thin compact myocardial layer   (MGI Ref ID J:36567)
  • thin myocardium   (MGI Ref ID J:36567)
  • thin ventricular wall
    • in some homozygotes, the nontrabeculated ventricular myocardium is composed of only a single cell layer; in contrast, the endocardial and epicardial layers appear normal   (MGI Ref ID J:36567)
  • ventricular hypoplasia
    • at E12.5-E15.5, homozygotes display hypoplasia of both the right and left ventricles   (MGI Ref ID J:36567)
  • growth/size/body phenotype
  • decreased embryo size   (MGI Ref ID J:36567)
  • fetal growth retardation
    • at E15.5, homozygotes display an overall developmental delay of ~24-36 hr relative to wild-type embryos   (MGI Ref ID J:36567)
  • muscle phenotype
  • abnormal myocardial trabeculae morphology
    • at E12.5-E15.5, homozygotes display abnormally thinned trabeculae in the ventricles and atria   (MGI Ref ID J:36567)
    • trabecula carnea hypoplasia
      • at E12.5-E15.5, homozygotes show disorganized trabeculae in the ventricular wall   (MGI Ref ID J:36567)
  • decreased ventricle muscle contractility
    • at E12.5-E13.5, homozygotes display a >70% decrease in left ventricular ejection fraction, indicating ventricular chamber dysfunction   (MGI Ref ID J:36567)
  • embryogenesis phenotype
  • decreased embryo size   (MGI Ref ID J:36567)
  • integument phenotype
  • pallor
    • at E15.5, homozygotes exhibit a normal liver but are generally paler than wild-type or heterozygous embryos, suggesting inadequate vascular irrigation   (MGI Ref ID J:36567)
View Research Applications

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

Cardiovascular Research
Heart Abnormalities

Developmental Biology Research
Embryonic Lethality (Homozygous)
Internal/Organ Defects
      heart

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Adrbk1tm1Mca
Allele Name targeted mutation 1, Marc Caron
Allele Type Targeted (Null/Knockout)
Common Name(s) GRK2-; betaARK1-;
Mutation Made By Marc Caron,   Duke University Medical Center
Strain of Origin129
Gene Symbol and Name Adrbk1, adrenergic receptor kinase, beta 1
Chromosome 19
Gene Common Name(s) Adrbk-1; BARK1; BETA-ARK1; Bark-1; GRK-2; GRK2; beta ARK; beta ARK1; beta-AR kinase-1; beta-adrenergic receptor kinase 1; beta-adrenergic receptor kinase-1; betaARK1;
Molecular Note A neomycin cassette replaced exons 5 through 8, encoding catalytic subdomain I that contains a portion of an ATP-binding site. The insertion also altered the downstream reading frame. Northern blot analysis of mutant embryos showed a 62% reduction of transcripts in heterozygotes and an absence of transcripts in homozygotes. Western blot analysis showed correlative results. [MGI Ref ID J:36567]

Genotyping

Genotyping Information

Genotyping Protocols

Adrbk1tm1Mca, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Jaber M; Koch WJ; Rockman H; Smith B; Bond RA; Sulik KK; Ross J Jr; Lefkowitz RJ; Caron MG; Giros B. 1996. Essential role of beta-adrenergic receptor kinase 1 in cardiac development and function. Proc Natl Acad Sci U S A 93(23):12974-9. [PubMed: 8917529]  [MGI Ref ID J:36567]

Additional References

Adrbk1tm1Mca related

Arnon TI; Xu Y; Lo C; Pham T; An J; Coughlin S; Dorn GW; Cyster JG. 2011. GRK2-dependent S1PR1 desensitization is required for lymphocytes to overcome their attraction to blood. Science 333(6051):1898-903. [PubMed: 21960637]  [MGI Ref ID J:176118]

Cho MC; Rao M; Koch WJ; Thomas SA; Palmiter RD; Rockman HA. 1999. Enhanced contractility and decreased beta-adrenergic receptor kinase-1 in mice lacking endogenous norepinephrine and epinephrine. Circulation 99(20):2702-7. [PubMed: 10338466]  [MGI Ref ID J:55312]

Eijkelkamp N; Heijnen CJ; Willemen HL; Deumens R; Joosten EA; Kleibeuker W; den Hartog IJ; van Velthoven CT; Nijboer C; Nassar MA; Dorn GW 2nd; Wood JN; Kavelaars A. 2010. GRK2: a novel cell-specific regulator of severity and duration of inflammatory pain. J Neurosci 30(6):2138-49. [PubMed: 20147541]  [MGI Ref ID J:157847]

Garcia-Guerra L; Nieto-Vazquez I; Vila-Bedmar R; Jurado-Pueyo M; Zalba G; Diez J; Murga C; Fernandez-Veledo S; Mayor F Jr; Lorenzo M. 2010. G protein-coupled receptor kinase 2 plays a relevant role in insulin resistance and obesity. Diabetes 59(10):2407-17. [PubMed: 20627936]  [MGI Ref ID J:169625]

Kleibeuker W; Ledeboer A; Eijkelkamp N; Watkins LR; Maier SF; Zijlstra J; Heijnen CJ; Kavelaars A. 2007. A role for G protein-coupled receptor kinase 2 in mechanical allodynia. Eur J Neurosci 25(6):1696-704. [PubMed: 17408432]  [MGI Ref ID J:122912]

Nijboer CH; Heijnen CJ; Degos V; Willemen HL; Gressens P; Kavelaars A. 2013. Astrocyte GRK2 as a novel regulator of glutamate transport and brain damage. Neurobiol Dis 54:206-15. [PubMed: 23313319]  [MGI Ref ID J:197760]

Nijboer CH; Kavelaars A; Vroon A; Groenendaal F; van Bel F; Heijnen CJ. 2008. Low endogenous G-protein-coupled receptor kinase 2 sensitizes the immature brain to hypoxia-ischemia-induced gray and white matter damage. J Neurosci 28(13):3324-32. [PubMed: 18367599]  [MGI Ref ID J:133493]

Penela P; Ribas C; Aymerich I; Eijkelkamp N; Barreiro O; Heijnen CJ; Kavelaars A; Sanchez-Madrid F; Mayor F Jr. 2008. G protein-coupled receptor kinase 2 positively regulates epithelial cell migration. EMBO J 27(8):1206-18. [PubMed: 18369319]  [MGI Ref ID J:134269]

Rajagopal K; Whalen EJ; Violin JD; Stiber JA; Rosenberg PB; Premont RT; Coffman TM; Rockman HA; Lefkowitz RJ. 2006. Beta-arrestin2-mediated inotropic effects of the angiotensin II type 1A receptor in isolated cardiac myocytes. Proc Natl Acad Sci U S A 103(44):16284-9. [PubMed: 17060617]  [MGI Ref ID J:115598]

Rakesh K; Yoo B; Kim IM; Salazar N; Kim KS; Rockman HA. 2010. beta-Arrestin-biased agonism of the angiotensin receptor induced by mechanical stress. Sci Signal 3(125):ra46. [PubMed: 20530803]  [MGI Ref ID J:185409]

Rivas V; Carmona R; Munoz-Chapuli R; Mendiola M; Nogues L; Reglero C; Miguel-Martin M; Garcia-Escudero R; Dorn GW 2nd; Hardisson D; Mayor F Jr; Penela P. 2013. Developmental and tumoral vascularization is regulated by G protein-coupled receptor kinase 2. J Clin Invest 123(11):4714-30. [PubMed: 24135140]  [MGI Ref ID J:204684]

Rockman HA; Choi DJ; Akhter SA; Jaber M; Giros B; Lefkowitz RJ; Caron MG; Koch WJ. 1998. Control of myocardial contractile function by the level of beta-adrenergic receptor kinase 1 in gene-targeted mice. J Biol Chem 273(29):18180-4. [PubMed: 9660778]  [MGI Ref ID J:48681]

Tarrant TK; Rampersad RR; Esserman D; Rothlein LR; Liu P; Premont RT; Lefkowitz RJ; Lee DM; Patel DD. 2008. Granulocyte chemotaxis and disease expression are differentially regulated by GRK subtype in an acute inflammatory arthritis model (K/BxN). Clin Immunol 129(1):115-22. [PubMed: 18662895]  [MGI Ref ID J:140405]

Vila-Bedmar R; Garcia-Guerra L; Nieto-Vazquez I; Mayor F Jr; Lorenzo M; Murga C; Fernandez-Veledo S. 2012. GRK2 contribution to the regulation of energy expenditure and brown fat function. FASEB J 26(8):3503-14. [PubMed: 22516294]  [MGI Ref ID J:187470]

Vroon A; Heijnen CJ; Lombardi MS; Cobelens PM; Mayor F Jr; Caron MG; Kavelaars A. 2004. Reduced GRK2 level in T cells potentiates chemotaxis and signaling in response to CCL4. J Leukoc Biol 75(5):901-9. [PubMed: 14761932]  [MGI Ref ID J:89443]

Vroon A; Kavelaars A; Limmroth V; Lombardi MS; Goebel MU; Van Dam AM; Caron MG; Schedlowski M; Heijnen CJ. 2005. G protein-coupled receptor kinase 2 in multiple sclerosis and experimental autoimmune encephalomyelitis. J Immunol 174(7):4400-6. [PubMed: 15778405]  [MGI Ref ID J:110002]

del Rey A; Renigunta V; Dalpke AH; Leipziger J; Matos JE; Robaye B; Zuzarte M; Kavelaars A; Hanley PJ. 2006. Knock-out mice reveal the contributions of P2Y and P2X receptors to nucleotide-induced Ca2+ signaling in macrophages. J Biol Chem 281(46):35147-55. [PubMed: 16980298]  [MGI Ref ID J:117254]

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 maintained as a live colony, heterozygotes may be bred. Wildtype x heterozygote crosses, but not heterozygote x heterozygote crosses are recommended by the donating investigator. Homozygotes die before birth.

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
   Wild-type from the colony
   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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