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 Background Strain C57BL/6 Donor Strain 129S2 via D3H ES cell line Generation pF3N1p Generation Definitions   Donating Investigator Lee Limbird,   Vanderbilt University School of Medicine

Appearance
black
Related Genotype: a/a

Description
Mice homozygous for this mutation are viable and fertile. They exhibit loss of physiological functions evoked by alpha2-adrenergic receptor agonists and display increased susceptibility to kindling-induced seizures.

Development
The Adra2a^tm1Lel targeted mutation made by Dr. Lee Limbird. The "hit and run" gene targeting technique was used to generate a D79N mutation in the Adra2a gene.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Adra2a

004367

B6.129-Adra2atm1Bkk/J

View Strains carrying other alleles of Adra2a     (1 strain)

Additional Web Information

Genetic Quality Control Annual Report

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.

Adra2a^tm1Lel/Adra2a^tm1Lel

        involves: 129S2/SvPas * C57BL/6

• cardiovascular system phenotype
• abnormal systemic arterial blood pressure
  • homozygotes are viable and exhibit normal baseline blood pressure and heart rate relative to wild-type mice   (MGI Ref ID J:34820)
  • however, unlike wild-type mice, homozygotes fail to exhibit an immediate (transient) hypertensive response after femoral administration of alpha2AR agonist UK14,304   (MGI Ref ID J:34820)
  • in addition, homozygotes fail to exhibit a subsequent hypotensive response to alpha2AR agonists, independent of the agonist used (UK14,304 or dexmedetomidine) or the site of agonist infusion (carotid or femoral)   (MGI Ref ID J:34820)

View Research Applications

Research Applications

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

Sensorineural Research
Nociception

Adra2a^tm1Lel related

Cardiovascular Research
Heart Abnormalities
      tachycardia
Hypotension

Neurobiology Research
Epilepsy

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Adra2atm1Lel
Allele Name		targeted mutation 1, Lee E Limbird
Allele Type		Targeted (knock-out)
Common Name(s)		D79N; alpha2A-ARD79N;
Mutation Made By		Lee Limbird,   Vanderbilt University School of Medicine
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3H
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Adra2a, adrenergic receptor, alpha 2a
Chromosome		19
Gene Common Name(s)		ADRA2; ADRA2R; ADRAR; ALPHA2AAR; AW122659; Adra-2; Adra-2a; CA2-47; RATRG20; RG20; ZNF32; adrenergic receptor, alpha 2; alpha(2A)AR; alpha2A; alpha2A-AR; alpha2A-adrenergic receptor; expressed sequence AW122659;
Molecular Note		Point mutations were introduced to alter the codon at position 79 from one encoding aspartic acid to one encoding asparagine. RNase protection assays indicated that normal levels of transcript were produced from this allele, but binding assays indicatedthat no functional protein was present in isolated brain membranes of homozygous mice. [MGI Ref ID J:34820]

Genotyping

Genotyping Information

Genotyping Protocols

Adra2a^tm1Lel, Restriction Enzyme Digest
Adra2a^tm1Lel, Restriction Enzyme Digest

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

MacMillan LB; Hein L; Smith MS; Piascik MT; Limbird LE. 1996. Central hypotensive effects of the alpha2a-adrenergic receptor subtype. Science 273(5276):801-3. [PubMed: 8670421]  [MGI Ref ID J:34820]

Additional References

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]

Janumpalli S; Butler LS; MacMillan LB; Limbird LE; McNamara JO. 1998. A point mutation (D79N) of the alpha2A adrenergic receptor abolishes the antiepileptogenic action of endogenous norepinephrine. J Neurosci 18(6):2004-8. [PubMed: 9482787]  [MGI Ref ID J:46771]

Lakhlani PP; MacMillan LB; Guo TZ; McCool BA; Lovinger DM; Maze M ; Limbird LE. 1997. Substitution of a mutant alpha2a-adrenergic receptor via hit and run gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo. Proc Natl Acad Sci U S A 94(18):9950-5. [PubMed: 9275232]  [MGI Ref ID J:42812]

Tolentino-Silva FP; Haxhiu MA; Waldbaum S; Dreshaj IA; Ernsberger P. 2000. alpha(2)-adrenergic receptors are not required for central anti-hypertensive action of moxonidine in mice. Brain Res 862(1-2):26-35. [PubMed: 10799665]  [MGI Ref ID J:61820]

Adra2a^tm1Lel 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]

Cleary L; Vandeputte C; Docherty JR. 2002. Investigation of neurotransmission in vas deferens from alpha(2A/D)-adrenoceptor knockout mice. Br J Pharmacol 136(6):857-64. [PubMed: 12110610]  [MGI Ref ID J:103269]

Davies MF; Tsui JY; Flannery JA; Li X; DeLorey TM; Hoffman BB. 2003. Augmentation of the noradrenergic system in alpha-2 adrenergic receptor deficient mice: anatomical changes associated with enhanced fear memory. Brain Res 986(1-2):157-65. [PubMed: 12965240]  [MGI Ref ID J:107779]

Franowicz JS; Kessler LE; Borja CM; Kobilka BK; Limbird LE; Arnsten AF. 2002. Mutation of the alpha2A-adrenoceptor impairs working memory performance and annuls cognitive enhancement by guanfacine. J Neurosci 22(19):8771-7. [PubMed: 12351753]  [MGI Ref ID J:111349]

Janumpalli S; Butler LS; MacMillan LB; Limbird LE; McNamara JO. 1998. A point mutation (D79N) of the alpha2A adrenergic receptor abolishes the antiepileptogenic action of endogenous norepinephrine. J Neurosci 18(6):2004-8. [PubMed: 9482787]  [MGI Ref ID J:46771]

Kingery WS; Guo TZ; Davies MF; Limbird L; Maze M. 2000. The alpha(2A) adrenoceptor and the sympathetic postganglionic neuron contribute to the development of neuropathic heat hyperalgesia in mice Pain 85(3):345-58. [PubMed: 10781908]  [MGI Ref ID J:62345]

Lakhlani PP; MacMillan LB; Guo TZ; McCool BA; Lovinger DM; Maze M ; Limbird LE. 1997. Substitution of a mutant alpha2a-adrenergic receptor via hit and run gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo. Proc Natl Acad Sci U S A 94(18):9950-5. [PubMed: 9275232]  [MGI Ref ID J:42812]

Peng N; Chambless BD; Oparil S; Wyss JM. 2003. Alpha2A-adrenergic receptors mediate sympathoinhibitory responses to atrial natriuretic peptide in the mouse anterior hypothalamic nucleus. Hypertension 41(3):571-5. [PubMed: 12623961]  [MGI Ref ID J:131890]

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]

Schramm NL; McDonald MP; Limbird LE. 2001. The alpha(2a)-adrenergic receptor plays a protective role in mouse behavioral models of depression and anxiety. J Neurosci 21(13):4875-82. [PubMed: 11425914]  [MGI Ref ID J:70077]

Tan CM; Wilson MH; MacMillan LB; Kobilka BK; Limbird LE. 2002. Heterozygous alpha 2A-adrenergic receptor mice unveil unique therapeutic benefits of partial agonists. Proc Natl Acad Sci U S A 99(19):12471-6. [PubMed: 12205290]  [MGI Ref ID J:127138]

TeKippe M; Harrison DE; Chen J. 2003. Expansion of hematopoietic stem cell phenotype and activity in Trp53-null mice. Exp Hematol 31(6):521-7. [PubMed: 12829028]  [MGI Ref ID J:115677]

Vandeputte C; Docherty JR. 2002. Modulation of contraction by alpha(2A/D)-adrenoceptors in mouse aorta: evidence employing knockout technology. Br J Pharmacol 135(5):1209-12. [PubMed: 11877328]  [MGI Ref ID J:103201]

Zhu QM; Lesnick JD; Jasper JR; MacLennan SJ; Dillon MP; Eglen RM; Blue DR Jr. 1999. Cardiovascular effects of rilmenidine, moxonidine and clonidine in conscious wild-type and D79N alpha2A-adrenoceptor transgenic mice. Br J Pharmacol 126(6):1522-30. [PubMed: 10217548]  [MGI Ref ID J:56221]

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.

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

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
	000664 C57BL/6J
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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