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 Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation ?+N1p (20-FEB-05) Generation Definitions   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

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

Related Strains

Strains carrying other alleles of Adra2b

008073

FVB-Tg(PDGFB-Adra2b)13Hag/J

View Strains carrying other alleles of Adra2b     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Adra2b^tm1Gsb/Adra2b^tm1Gsb

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

• mortality/aging
• postnatal lethality
  • homozygous null mice were viable, fertile and grossly normal, but were recovered from heterozygous crosses at less than the predicted Mendelian ratios   (MGI Ref ID J:34819)
  • homozygous null mice displayed poorer survival; no specific reason for this poor survival has been reported   (MGI Ref ID J:34819)
• behavior/neurological phenotype
• *normal* behavior/neurological phenotype
  • in response to dexmedetomidine, homozygous null mice showed normal dose-dependent reductions in locomotor activity   (MGI Ref ID J:89316)
  • also, dexmedetomidine induced normal dose-dependent antinociception in homozygous null mice in the hot-water tail immersion test   (MGI Ref ID J:89316)
• cardiovascular system phenotype
• *normal* cardiovascular system phenotype
  • unrestrained, conscious mutant animals displayed no significant changes in mean arterial pressure or heart rate at baseline   (MGI Ref ID J:34819)
  • 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   (MGI Ref ID J:89317)
• • abnormal vasoconstriction
    • notably, mutant mice exhibited an absence of alpha2-mediated peripheral vasoconstriction   (MGI Ref ID J:34819)
    • 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   (MGI Ref ID J:34819)
    • 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   (MGI Ref ID J:34819)
• homeostasis/metabolism phenotype
• *normal* homeostasis/metabolism phenotype
  • in response to dexmedetomidine, homozygous null mice showed normal dose-dependent reductions in body temperature   (MGI Ref ID J:89316)
• reproductive system phenotype
• abnormal fertility/fecundity
  • homozygous null mice did not breed well compared with wild-type littermates   (MGI Ref ID J:34819)
  • 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   (MGI Ref ID J:58591)
• muscle phenotype
• abnormal vasoconstriction
  • notably, mutant mice exhibited an absence of alpha2-mediated peripheral vasoconstriction   (MGI Ref ID J:34819)
  • 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   (MGI Ref ID J:34819)
  • 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   (MGI Ref ID J:34819)

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
  • 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)   (MGI Ref ID J:89315)
  • consistent with these findings, direct mean arterial pressure was significantly lower in subtotally nephrectomized heterozygous mutant mice relative to wild-type littermates   (MGI Ref ID J:89315)
  • 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   (MGI Ref ID J:89315)
• renal/urinary system phenotype
• *normal* renal/urinary system phenotype
  • 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   (MGI Ref ID J:89315)

Adra2b^tm1Gsb/Adra2b^tm1Gsb

        B6.129-Adra2b^tm1Gsb

• mortality/aging
• partial neonatal lethality
  • most homozygotes die during the day of birth; however, normal Mendelian ratios are obtained between E10.5 and E18.5   (MGI Ref ID J:166788)
  • treatment of pregnant mice with cyclopamine (a smoothened antagonist) from E17.5 significantly increases the % of homozygotes surviving the immediate neonatal period   (MGI Ref ID J:166788)
• growth/size phenotype
• decreased birth weight
  • at P0, body weight is significantly lower than that in wild-type controls   (MGI Ref ID J:166788)
• slow postnatal weight gain
  • newborn homozygotes gain weight more slowly than wild-type controls   (MGI Ref ID J:166788)
  • however, drinking behavior is normal, as shown by the presence of gastric milk   (MGI Ref ID J:166788)
• homeostasis/metabolism phenotype
• cyanosis
  • homozygotes become cyanotic within hours of birth   (MGI Ref ID J:166788)
• respiratory system phenotype
• abnormal lung development
  • homozygotes show an early postnatal defect in lung maturation due to enhanced sonic hedgehog (SHH) signaling   (MGI Ref ID J:166788)
  • however, pulmonary vascular development is not significantly altered as shown by normal capillary density   (MGI Ref ID J:166788)
• • increased mesenchymal cell proliferation involved in lung development
    • enhanced sonic hedgehog (SHH) signaling results in increased mesenchymal proliferation   (MGI Ref ID J:166788)
    • at P0, mutant lungs show a significant increase in the rate of mitosis and expression of cell cycle regulators cyclin D1 and Ki67 relative to wild-type lungs   (MGI Ref ID J:166788)
    • inhibition of enhanced SHH signaling by the smoothened antagonist cyclopamine rescues the lung morphology and altered gene expression in P1 mutant mice   (MGI Ref ID J:166788)
• abnormal pulmonary alveolus morphology
  • several hours after birth, homozygotes display reduced alveolar spaces relative to wild-type controls   (MGI Ref ID J:166788)
• atelectasis
  • early after birth, mutant lungs are less inflated than wild-type lungs   (MGI Ref ID J:166788)
• decreased lung weight
  • at P0, lung weight is significantly lower than that in wild-type controls   (MGI Ref ID J:166788)
• respiratory failure
  • homozygotes exhibit early postnatal respiratory failure   (MGI Ref ID J:166788)
  • however, a normal spontaneous breathing rate is observed immediately after birth   (MGI Ref ID J:166788)
• thick pulmonary interalveolar septum
  • several hours after birth, homozygotes display thickened interalveolar septae relative to wild-type controls   (MGI Ref ID J:166788)
• cardiovascular system phenotype
• dilated heart right ventricle
  • at P0, the right ventricle is significantly dilated relative to that in wild-type hearts   (MGI Ref ID J:166788)
  • however, cardiac structure and function is normal with no significant differences in cardiac rhythm, ECG recordings or closure of the ductus arteriosus relative to wild-type controls   (MGI Ref ID J:166788)
• hematopoietic system phenotype
• *normal* hematopoietic system phenotype
  • at P0, homozygotes display normal erythrocyte counts and morphology as well as normal hemoglobin synthesis relative to wild-type controls   (MGI Ref ID J:166788)
• cellular phenotype
• increased mesenchymal cell proliferation involved in lung development
  • enhanced sonic hedgehog (SHH) signaling results in increased mesenchymal proliferation   (MGI Ref ID J:166788)
  • at P0, mutant lungs show a significant increase in the rate of mitosis and expression of cell cycle regulators cyclin D1 and Ki67 relative to wild-type lungs   (MGI Ref ID J:166788)
  • inhibition of enhanced SHH signaling by the smoothened antagonist cyclopamine rescues the lung morphology and altered gene expression in P1 mutant mice   (MGI Ref ID J:166788)

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 provided by MGI

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; alpha2B;
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, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

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]

Haubold M; Gilsbach R; Hein L. 2010. {Alpha}2B-adrenoceptor deficiency leads to postnatal respiratory failure in mice. J Biol Chem 285(44):34213-9. [PubMed: 20729197]  [MGI Ref ID J:166788]

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]

Hocker J; Gruenewald M; Meybohm P; Schaper C; Scholz J; Steinfath M; Bein B. 2010. Nefopam but not physostigmine affects the thermoregulatory response in mice via alpha(2)-adrenoceptors. Neuropharmacology 58(2):495-500. [PubMed: 19744502]  [MGI Ref ID J:179564]

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]

Muthig V; Gilsbach R; Haubold M; Philipp M; Ivacevic T; Gessler M; Hein L. 2007. Upregulation of soluble vascular endothelial growth factor receptor 1 contributes to angiogenesis defects in the placenta of alpha 2B-adrenoceptor deficient mice. Circ Res 101(7):682-91. [PubMed: 17673674]  [MGI Ref ID J:141347]

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

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.
• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	See control note:	C57BL/6J mice (Stock No. 000664) may be used as controls.
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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.

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