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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.
| C57BL/6J mice (Stock No. 000664) may be used as controls. | ||
| Considerations for Choosing Controls | ||
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
Adra2btm1Gsb/Adra2btm1Gsb
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.
Adra2btm1Gsb/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:Adra2btm1Gsb related
Cardiovascular Research
Vascular Defects
| 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 Protocols
Adra2btm1Gsb, STD PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
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]
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]
Adra2btm1Gsb relatedAihara 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]
Currently there no information available for this strain. This may be due to the supply level of this strain.
| Pricing for USA, Canada and Mexico shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $1900.00 Cryopreserved Embryos Fee $1600.00
| Pricing for International shipping destinations |
|
*Price(s) in US dollars ($)
Weeks of Age Price* Gender Cryorecovery Fee $2470.00 Cryopreserved Embryos Fee $2080.00
| Standard Supply | Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information. |
|---|---|
| Supply Notes |
|
| 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. | ||
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