Description

Strain Information

Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse   Donating Investigator Brian Kobilka,   Stanford University

Description
Homozygotes are viable and fertile. They exhibit an absence of alpha2-mediated peripheral vasoconstriction.

Development
This strain is maintained by mating homozygotes.

Control Information

		C57BL/6J mice (Stock No. 000664) may be used as controls.
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

Adra2b^tm1Gsb/Adra2b^tm1Gsb

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

• lethality-postnatal
• postnatal lethality (MGI Ref ID J:34819)
  • homozygous null mice were viable, fertile and grossly normal, but were recovered from heterozygous crosses at less than the predicted Mendelian ratios
  • homozygous null mice displayed poorer survival; no specific reason for this poor survival has been reported
• behavior/neurological phenotype
• *normal* behavior/neurological phenotype (MGI Ref ID J:89316)
  • in response to dexmedetomidine, homozygous null mice showed normal dose-dependent reductions in locomotor activity
  • also, dexmedetomidine induced normal dose-dependent antinociception in homozygous null mice in the hot-water tail immersion test
• cardiovascular system phenotype
• *normal* cardiovascular system phenotype (MGI Ref ID J:34819)
  • unrestrained, conscious mutant animals displayed no significant changes in mean arterial pressure or heart rate at baseline
  • when subjected to bilateral nephrectomy followed by acute saline loading, anephric homozygous null mice were unable to raise their blood pressure, as expected, and displayed a slightly lowered blood pressure at the end of the infusion period, despite significantly elevated levels of norepinephrine in these mice
• abnormal vasoconstriction (MGI Ref ID J:34819)
  • notably, mutant mice exhibited an absence of alpha2-mediated peripheral vasoconstriction
  • specifically, in wild-type mice, the arterial blood pressure response to dexmedetomidine (an alpha2-adrenergic receptor agonist) was typified by an immediate hypertensive response, followed by a long-lasting hypotensive response, as well as an immediate bradycardia; in contrast, in homozygous null mice, the hypertensive response was abolished, and the hypotensive effect was immediate and accentuated, whereas the bradycardic response was normal relative to wild-type
  • homozygous null mice exhibited a normal hypertensive response to challenge with a non-selective alpha1 agonist (phenylephrine), indicating a normal vasoconstrictive response to alpha1-adrenergic receptor stimulation
• homeostasis/metabolism phenotype
• *normal* homeostasis/metabolism phenotype (MGI Ref ID J:89316)
  • in response to dexmedetomidine, homozygous null mice showed normal dose-dependent reductions in body temperature
• reproductive system phenotype
• abnormal fertility/fecundity (MGI Ref ID J:34819)
  • homozygous null mice did not breed well compared with wild-type littermates
  • poor survival and breeding suggesting some developmental or reproductive deficit was corroborated by the inability to produce either Adra2a/Adra2b or Adra2b/Adra2c double homozygous null mice

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

Adra2b^tm1Gsb/Adra2b⁺

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

• cardiovascular system phenotype
• *normal* cardiovascular system phenotype (MGI Ref ID J:89315)
  • when subjected to subtotal nephrectomy followed by dietary salt loading, heterozygous mutant mice displayed an attenuated hypertensive response, resulting in a significantly lower end-point tail-cuff blood pressure compared with their wild-type controls and a significantly lower change in blood pressure (8.1±2.44 versus 39.4±6.83 mm Hg, respectively)
  • consistent with these findings, direct mean arterial pressure was significantly lower in subtotally nephrectomized heterozygous mutant mice relative to wild-type littermates
  • heterozygous mutant mice displayed no difference in baseline blood pressure (prior to subtotal nephrectomy) relative to wild-type littermates; similarly, heterozygotes showed no difference in baseline or end-point heart rate relative to wild-type littermates
• renal/urinary system phenotype
• *normal* renal/urinary system phenotype (MGI Ref ID J:89315)
  • subtotally nephrectomized heterozygous mutant mice that were given 1% saline as drinking water showed no changes in body weight, ratio of remnant kidney weight to body weight, or plasma creatinine levels relative to wild-type littermates

View Research Applications

Research Applications

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

Adra2b^tm1Gsb related

Cardiovascular Research
Vascular Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Adra2btm1Gsb
Allele Name		targeted mutation 1, Gregory S Barsh
Allele Type		Targeted (knock-out)
Common Name(s)		alpha2B-; alpha2B-KO;
Mutation Made By		Brian Kobilka,   Stanford University
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Adra2b, adrenergic receptor, alpha 2b
Chromosome		2
Gene Common Name(s)		ADRA2L1; ADRA2RL1; ADRARL1; ALPHA2BAR; Adra-2b; [a]2B; alpha2-C2; alpha2B; subtype alpha2-C2;
Molecular Note		A neomycin selection cassette was inserted into the coding sequences, placing a premature stop codon before the sequences encoding the fifth transmembrane domain. Western blot analysis on kidney membrane extracts confirmed that the protein was not detectable in homozygous mice. [MGI Ref ID J:34819]

Genotyping

Genotyping Information

Genotyping Protocols

Adra2b^tm1Gsb, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Link RE; Kobilka BK; Barsh GS. 1993. Linkage mapping of alpha-2 adrenergic receptor genes to mouse chromosomes 2 and 5. Mamm Genome 4(11):650-5. [PubMed: 8281014]  [MGI Ref ID J:15640]

Additional References

Link RE; Desai K; Hein L; Stevens ME; Chruscinski A; Bernstein D; Barsh GS; Kobilka BK. 1996. Cardiovascular regulation in mice lacking alpha2-adrenergic receptor subtypes b and c. Science 273(5276):803-5. [PubMed: 8670422]  [MGI Ref ID J:34819]

Adra2b^tm1Gsb related

Aihara M; Lindsey JD; Weinreb RN. 2008. Effect on diurnal intraocular pressure variation of eliminating the alpha-2 adrenergic receptor subtypes in the mouse. Invest Ophthalmol Vis Sci 49(3):929-33. [PubMed: 18326714]  [MGI Ref ID J:133027]

Altman JD; Trendelenburg AU; MacMillan L; Bernstein D; Limbird L; Starke K; Kobilka BK; Hein L. 1999. Abnormal regulation of the sympathetic nervous system in alpha2A-adrenergic receptor knockout mice. Mol Pharmacol 56(1):154-61. [PubMed: 10385696]  [MGI Ref ID J:76317]

Brede M; Nagy G; Philipp M; Sorensen JB; Lohse MJ; Hein L. 2003. Differential control of adrenal and sympathetic catecholamine release by alpha 2-adrenoceptor subtypes. Mol Endocrinol 17(8):1640-6. [PubMed: 12764077]  [MGI Ref ID J:126731]

Bucheler MM; Hadamek K; Hein L. 2002. Two alpha(2)-adrenergic receptor subtypes, alpha(2A) and alpha(2C), inhibit transmitter release in the brain of gene-targeted mice. Neuroscience 109(4):819-26. [PubMed: 11927164]  [MGI Ref ID J:126644]

Duling LC; Cherng TW; Griego JR; Perrine MF; Kanagy NL. 2006. Loss of alpha2B-adrenoceptors increases magnitude of hypertension following nitric oxide synthase inhibition. Am J Physiol Heart Circ Physiol 291(5):H2403-8. [PubMed: 16815979]  [MGI Ref ID J:116281]

Hein L; Altman JD; Kobilka BK. 1999. Two functionally distinct alpha2-adrenergic receptors regulate sympathetic neurotransmission. Nature 402(6758):181-4. [PubMed: 10647009]  [MGI Ref ID J:58591]

Hunter JC; Fontana DJ; Hedley LR; Jasper JR; Lewis R; Link RE; Secchi R; Sutton J; Eglen RM. 1997. Assessment of the role of alpha2-adrenoceptor subtypes in the antinociceptive, sedative and hypothermic action of dexmedetomidine in transgenic mice. Br J Pharmacol 122(7):1339-44. [PubMed: 9421280]  [MGI Ref ID J:89316]

Kable JW; Murrin LC; Bylund DB. 2000. In vivo gene modification elucidates subtype-specific functions of alpha(2)-adrenergic receptors. J Pharmacol Exp Ther 293(1):1-7. [PubMed: 10734146]  [MGI Ref ID J:89318]

Knaus A; Zong X; Beetz N; Jahns R; Lohse MJ; Biel M; Hein L. 2007. Direct inhibition of cardiac hyperpolarization-activated cyclic nucleotide-gated pacemaker channels by clonidine. Circulation 115(7):872-80. [PubMed: 17261653]  [MGI Ref ID J:132333]

Link RE; Desai K; Hein L; Stevens ME; Chruscinski A; Bernstein D; Barsh GS; Kobilka BK. 1996. Cardiovascular regulation in mice lacking alpha2-adrenergic receptor subtypes b and c. Science 273(5276):803-5. [PubMed: 8670422]  [MGI Ref ID J:34819]

Makaritsis KP; Handy DE; Johns C; Kobilka B; Gavras I; Gavras H. 1999. Role of the alpha2B-adrenergic receptor in the development of salt-induced hypertension. Hypertension 33(1):14-7. [PubMed: 9931075]  [MGI Ref ID J:89315]

Makaritsis KP; Johns C; Gavras I; Gavras H. 2000. Role of alpha(2)-adrenergic receptor subtypes in the acute hypertensive response to hypertonic saline infusion in anephric mice. Hypertension 35(2):609-13. [PubMed: 10679505]  [MGI Ref ID J:89317]

Moura E; Afonso J; Hein L; Vieira-Coelho MA. 2006. Alpha2-adrenoceptor subtypes involved in the regulation of catecholamine release from the adrenal medulla of mice. Br J Pharmacol 149(8):1049-58. [PubMed: 17075569]  [MGI Ref ID J:135922]

Paris A; Philipp M; Tonner PH; Steinfath M; Lohse M; Scholz J; Hein L. 2003. Activation of alpha 2B-adrenoceptors mediates the cardiovascular effects of etomidate. Anesthesiology 99(4):889-95. [PubMed: 14508322]  [MGI Ref ID J:106006]

Philipp M; Brede ME; Hadamek K; Gessler M; Lohse MJ; Hein L. 2002. Placental alpha(2)-adrenoceptors control vascular development at the interface between mother and embryo. Nat Genet 31(3):311-5. [PubMed: 12068299]  [MGI Ref ID J:77486]

Sawamura S; Kingery WS; Davies MF; Agashe GS; Clark JD; Kobilka BK; Hashimoto T; Maze M. 2000. Antinociceptive action of nitrous oxide is mediated by stimulation of noradrenergic neurons in the brainstem and activation of [alpha]2B adrenoceptors. J Neurosci 20(24):9242-51. [PubMed: 11125002]  [MGI Ref ID J:120560]

Scheibner J; Trendelenburg AU; Hein L; Starke K. 2001. Alpha2-adrenoceptors modulating neuronal serotonin release: a study in alpha2-adrenoceptor subtype-deficient mice. Br J Pharmacol 132(4):925-33. [PubMed: 11181434]  [MGI Ref ID J:115396]

Takedachi M; Qu D; Ebisuno Y; Oohara H; Joachims ML; McGee ST; Maeda E; McEver RP; Tanaka T; Miyasaka M; Murakami S; Krahn T; Blackburn MR; Thompson LF. 2008. CD73-generated adenosine restricts lymphocyte migration into draining lymph nodes. J Immunol 180(9):6288-96. [PubMed: 18424752]  [MGI Ref ID J:134523]

Health & husbandry

Health & Colony Maintenance Information

Currently there no information available for this strain. This may be due to the supply level of this strain.

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryopreserved Embryos This strain is also available as cryopreserved embryos from our Repository. Orders for cryopreserved embryos are supplied subject to a signed agreement that must be returned to the Customer Service Department after order placement. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos from our repository, please visit our Cryopreserved Embryos web page. Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

		C57BL/6J mice (Stock No. 000664) may be used as controls.
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.

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Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
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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.