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   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 may relate to a genetic background differing from this JAX^® Mice strain.

Adrbk1^tm1Mca/Adrbk1^tm1Mca

        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 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 (knock-out)
Common Name(s)		GRK2-; betaARK1-;
Mutation Made By		Marc Caron,   Duke University Medical Center
Strain of Origin		129
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

Adrbk1^tm1Mca, 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

Adrbk1^tm1Mca 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; 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]

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 & Husbandry	When 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

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

See Terms of Use tab for General Terms and Conditions

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 Information
JAX^® Mice
Surgical and Preconditioning Services
JAX^® Services
Customer Services and Support
Tel: 1-800-422-6423 or 1-207-288-5845
Fax: 1-207-288-6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Strain(s) not available to companies or for-profit entities.

Contact information

General inquiries regarding Terms of Use

Contracts Administration

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

JAX^® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (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. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON'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, JACKSON will, at its option, provide credit or replacement for the mice or product received or the services provided.

No Liability

In no event shall JACKSON, 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 JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS or services from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE and PRODUCTS 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 JACKSON’s MICE, PRODUCTS or services. In addition, special terms and conditions of sale of certain MICE, PRODUCTS or services may be set forth separately in JACKSON 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 JACKSON, 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 JACKSON, 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 or services by JACKSON.