Strain Name:

B6.129-Adra2ctm1Gsb/J

Stock Number:

003557

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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.
Specieslaboratory mouse
Background Strain C57BL/6
Donor Strain 129 derived ES cell line
 
Donating Investigator IMR Colony,   The Jackson Laboratory

Description
Mice homozygous for the Adra2ctm1Gsb mutation are viable and fertile. They display no gross abnormalities and hemodynamic functions are normal. Homozygotes do show an abnormal response to anesthesia and analgesia. They have also been noted to display an abnormal gait.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for the strain above. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Control Information

  Control
   000664 C57BL/6J
 
  Considerations for Choosing Controls

Related Strains

Strains carrying   Adra2ctm1Gsb allele
002512   STOCK Adra2ctm1Gsb/J
View Strains carrying   Adra2ctm1Gsb     (1 strain)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Alpha-2c-Adrenergic Receptor; ADRA2C   (ADRA2C)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

The following phenotype information is associated with a similar, but not exact match to this JAX® Mice strain.

Adra2ctm1Gsb/Adra2ctm1Gsb

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2J
  • behavior/neurological phenotype
  • *normal* behavior/neurological phenotype
    • in response to dexmedetomidine, homozygous mutant mice showed normal dose-dependent reductions in locomotor activity   (MGI Ref ID J:89316)
    • also, dexmedetomidine induced normal dose-dependent antinociception in homozygous mutant mice in the hot-water tail immersion test   (MGI Ref ID J:89316)
    • in response to dexmedetomidine, homozygous mutant mice displayed no major differences in spontaneous locomotor activity or its diurnal rhythm relative to wild-type   (MGI Ref ID J:38466)
    • homozygous mutant mice showed no significant differences from wild-type mice in head twitches in response to dexmedetomidine   (MGI Ref ID J:49002)
    • homozygous mutant mice displayed decreased attack latency in the isolation-induced aggression paradigm; however, there was no significant difference in the overall number of attacks, and preisolation aggressive behavior was normal   (MGI Ref ID J:46923)
    • abnormal spatial working memory
      • homozygous mutant mice displayed attenuated performance in the T-maze delayed alternation task: in this paradigm, mutants showed normal dose-dependent reductions in non-perseverative errors and increased performance in response to dexmedetomidine   (MGI Ref ID J:53676)
      • homozygous mutant mice made more working memory errors after the change of the baited arm in radial arm maze; however, mutant and wild-type mice performed equally well after training   (MGI Ref ID J:89323)
      • dexmedetomidine attenuated the increase in spatial working memory errors after the change of the baited arm   (MGI Ref ID J:89323)
      • homozygous mutant and wild-type mice performed equally well in T-maze, and dexmedetomidine had no effect on this simple response learning   (MGI Ref ID J:89323)
    • behavioral despair
      • homozygous mutant mice produced stress-protective effects: they displayed decreased immobility in a modified version of Porsolt's forced swimming test, indicating attenuated behavioral despair   (MGI Ref ID J:59712)
      • also, homozygous mutants displayed attenuated elevation of plasma corticosterone after different stressors   (MGI Ref ID J:59712)
    • increased startle reflex
      • homozygous mutant mice displayed enhanced startle responses, and diminished prepulse inhibition (PPI) of the startle reflex   (MGI Ref ID J:46923)
  • cardiovascular system phenotype
  • *normal* cardiovascular system phenotype
    • compared with wild-type, adult homozygous mutant mice displayed no significant differences in the magnitude of the hypertensive, hypotensive, or bradycardic responses to dexmedetomidine, a highly selective alpha2-adrenergic receptor agonist   (MGI Ref ID J:34819)
  • homeostasis/metabolism phenotype
  • *normal* homeostasis/metabolism phenotype
    • in response to dexmedetomidine, homozygous mutant mice showed normal dose-dependent reductions in body temperature   (MGI Ref ID J:89316)
    • contrary to original findings, homozygous null mice were reported to show a significant attenuation of the hypothermic response induced by dexmedetomidine   (MGI Ref ID J:38466)
  • nervous system phenotype
  • *normal* nervous system phenotype
    • in homozygous mutant mice, the maximal inhibitory effect of brimonidine on norepinephrine release was normal, relative to wild-type mice   (MGI Ref ID J:58591)
    • in response to dexmedetomidine, homozygous mutant mice displayed normal dose-dependent reductions in brain monoamine turnover, with the exception of some minor but consistent changes, including slightly reduced levels of metabolites of dopamine (homovanillic acid), norepinephrine (3-methoxy-4-hydroxyphenylglycol), and serotonin (5-hydroxyindoleacetic acid)   (MGI Ref ID J:38466)
    • relative to wild-type mice, homozygous mutant mice displayed increased locomotor activity in response to amphetamine; this effect was more prominent in amphetamine-treated male mutants than in female mutants   (MGI Ref ID J:49002)
    • notably, dexmedetomidine failed to attenuate symptoms of the 5-hydroxytryptophan-induced serotonin syndrome in homozygous mutant mice   (MGI Ref ID J:49002)

Adra2ctm1Gsb/Adra2ctm1Gsb

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
  • nervous system phenotype
  • *normal* nervous system phenotype
    • mice exhibit normal epinephrine-induced reduction in burst frequency of induced epileptiform activity   (MGI Ref ID J:197965)
View Research Applications

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

Adra2ctm1Gsb related

Neurobiology Research
Receptor Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Adra2ctm1Gsb
Allele Name targeted mutation 1, Gregory S Barsh
Allele Type Targeted (Null/Knockout)
Common Name(s) alpha2C-; alpha2C-ARKO; alpha2C-KO;
Mutation Made ByDr. Brian Kobilka,   Stanford University
Strain of Origin(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line NameR1
ES Cell Line Strain(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name Adra2c, adrenergic receptor, alpha 2c
Chromosome 5
Gene Common Name(s) ADRA2L2; ADRA2RL2; ADRARL2; ALPHA2CAR; Adra-2c; [a]2C; alpha2-C4; alpha2C; subtype alpha2-C4;
Molecular Note A neomycin cassette was inserted into the single coding exon. Northern blot analysis and RT-PCR analysis did not detect functional transcript produced from this allele in homozygous mice. [MGI Ref ID J:29109] [MGI Ref ID J:77486]

Genotyping

Genotyping Information

Genotyping Protocols

Adra2ctm1Gsb, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Additional References

Adra2ctm1Gsb 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]

Bjorklund M; Sirvio J; Puolivali J; Sallinen J; Jakala P; Scheinin M; Kobilka BK; Riekkinen P Jr. 1998. Alpha2C-adrenoceptor-overexpressing mice are impaired in executing nonspatial and spatial escape strategies. Mol Pharmacol 54(3):569-76. [PubMed: 9730916]  [MGI Ref ID J:77292]

Bjorklund M; Siverina I; Heikkinen T; Tanila H; Sallinen J; Scheinin M; Riekkinen P Jr. 2001. Spatial working memory improvement by an alpha2-adrenoceptor agonist dexmedetomidine is not mediated through alpha2C-adrenoceptor. Prog Neuropsychopharmacol Biol Psychiatry 25(8):1539-54. [PubMed: 11642653]  [MGI Ref ID J:89323]

Bonaventure P; Nepomuceno D; Hein L; Sutcliffe JG; Lovenberg T; Hedlund PB. 2004. Radioligand binding analysis of knockout mice reveals 5-hydroxytryptamine(7) receptor distribution and uncovers 8-hydroxy-2-(di-n-propylamino)tetralin interaction with alpha(2) adrenergic receptors. Neuroscience 124(4):901-11. [PubMed: 15026130]  [MGI Ref ID J:89990]

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]

Brum PC; Kosek J; Patterson A; Bernstein D; Kobilka B. 2002. Abnormal cardiac function associated with sympathetic nervous system hyperactivity in mice. Am J Physiol Heart Circ Physiol 283(5):H1838-45. [PubMed: 12384461]  [MGI Ref ID J:108048]

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]

Bueno CR Jr; Ferreira JC; Pereira MG; Bacurau AV; Brum PC. 2010. Aerobic exercise training improves skeletal muscle function and Ca2+ handling-related protein expression in sympathetic hyperactivity-induced heart failure. J Appl Physiol 109(3):702-9. [PubMed: 20595538]  [MGI Ref ID J:185923]

Ferreira JC; Bacurau AV; Evangelista FS; Coelho MA; Oliveira EM; Casarini DE; Krieger JE; Brum PC. 2008. The role of local and systemic renin angiotensin system activation in a genetic model of sympathetic hyperactivity-induced heart failure in mice. Am J Physiol Regul Integr Comp Physiol 294(1):R26-32. [PubMed: 17977919]  [MGI Ref ID J:130320]

Gilsbach R; Brede M; Beetz N; Moura E; Muthig V; Gerstner C; Barreto F; Neubauer S; Vieira-Coelho MA; Hein L. 2007. Heterozygous alpha 2C-adrenoceptor-deficient mice develop heart failure after transverse aortic constriction. Cardiovasc Res 75(4):728-37. [PubMed: 17597596]  [MGI Ref ID J:162731]

Goldenstein BL; Nelson BW; Xu K; Luger EJ; Pribula JA; Wald JM; O'Shea LA; Weinshenker D; Charbeneau RA; Huang X; Neubig RR; Doze VA. 2009. Regulator of G protein signaling protein suppression of Galphao protein-mediated alpha2A adrenergic receptor inhibition of mouse hippocampal CA3 epileptiform activity. Mol Pharmacol 75(5):1222-30. [PubMed: 19225179]  [MGI Ref ID J:197965]

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]

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]

Link RE; Stevens MS; Kulatunga M; Scheinin M; Barsh GS; Kobilka BK. 1995. Targeted inactivation of the gene encoding the mouse alpha 2c-adrenoceptor homolog. Mol Pharmacol 48(1):48-55. [PubMed: 7623774]  [MGI Ref ID J:29109]

Medeiros A; Rolim NP; Oliveira RS; Rosa KT; Mattos KC; Casarini DE; Irigoyen MC; Krieger EM; Krieger JE; Negrao CE; Brum PC. 2008. Exercise training delays cardiac dysfunction and prevents calcium handling abnormalities in sympathetic hyperactivity-induced heart failure mice. J Appl Physiol 104(1):103-9. [PubMed: 17975126]  [MGI Ref ID J:147520]

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]

Moura E; Silva E; Serrao MP; Afonso J; Kozmus CE; Vieira-Coelho MA. 2012. alpha2C-Adrenoceptors modulate L-DOPA uptake in opossum kidney cells and in the mouse kidney. Am J Physiol Renal Physiol 303(7):F928-38. [PubMed: 22859407]  [MGI Ref ID J:188615]

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]

Oliveira RS; Ferreira JC; Gomes ER; Paixao NA; Rolim NP; Medeiros A; Guatimosim S; Brum PC. 2009. Cardiac anti-remodelling effect of aerobic training is associated with a reduction in the calcineurin/NFAT signalling pathway in heart failure mice. J Physiol 587(Pt 15):3899-910. [PubMed: 19505981]  [MGI Ref ID J:176793]

Paris A; Mantz J; Tonner PH; Hein L; Brede M; Gressens P. 2006. The effects of dexmedetomidine on perinatal excitotoxic brain injury are mediated by the alpha2A-adrenoceptor subtype. Anesth Analg 102(2):456-61. [PubMed: 16428542]  [MGI Ref ID J:134285]

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]

Puolivali J; Bjorklund M; Holmberg M; Ihalainen JA; Scheinin M; Tanila H. 2002. Alpha 2C-adrenoceptor mediated regulation of cortical EEG arousal. Neuropharmacology 43(8):1305-12. [PubMed: 12527480]  [MGI Ref ID J:97413]

Riccio O; Hurni N; Murthy S; Vutskits L; Hein L; Dayer A. 2012. Alpha2-adrenergic receptor activation regulates cortical interneuron migration. Eur J Neurosci 36(7):2879-87. [PubMed: 22805283]  [MGI Ref ID J:207652]

Rolim NP; Medeiros A; Rosa KT; Mattos KC; Irigoyen MC; Krieger EM; Krieger JE; Negrao CE; Brum PC. 2007. Exercise training improves the net balance of cardiac Ca2+ handling protein expression in heart failure. Physiol Genomics 29(3):246-52. [PubMed: 17244791]  [MGI Ref ID J:128677]

Sallinen J; Haapalinna A; MacDonald E; Viitamaa T; Lahdesmaki J; Rybnikova E; Pelto-Huikko M; Kobilka BK; Scheinin M. 1999. Genetic alteration of the alpha2-adrenoceptor subtype c in mice affects the development of behavioral despair and stress-induced increases in plasma corticosterone levels. Mol Psychiatry 4(5):443-52. [PubMed: 10523817]  [MGI Ref ID J:59712]

Sallinen J; Haapalinna A; Viitamaa T; Kobilka BK; Scheinin M. 1998. Adrenergic alpha2C-receptors modulate the acoustic startle reflex, prepulse inhibition, and aggression in mice. J Neurosci 18(8):3035-42. [PubMed: 9526020]  [MGI Ref ID J:46923]

Sallinen J; Haapalinna A; Viitamaa T; Kobilka BK; Scheinin M. 1998. D-amphetamine and L-5-hydroxytryptophan-induced behaviours in mice with genetically-altered expression of the alpha2C-adrenergic receptor subtype. Neuroscience 86(3):959-65. [PubMed: 9692731]  [MGI Ref ID J:49002]

Sallinen J; Link RE; Haapalinna A; Viitamaa T; Kulatunga M; Sjoholm B ; Macdonald E ; Pelto-Huikko M ; Leino T ; Barsh GS ; Kobilka BK ; Scheinin M. 1997. Genetic alteration of alpha 2C-adrenoceptor expression in mice: influence on locomotor, hypothermic, and neurochemical effects of dexmedetomidine, a subtype-nonselective alpha 2-adrenoceptor agonist. Mol Pharmacol 51(1):36-46. [PubMed: 9016344]  [MGI Ref ID J:38466]

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]

Tanila H; Mustonen K; Sallinen J; Scheinin M; Riekkinen P Jr. 1999. Role of alpha2C-adrenoceptor subtype in spatial working memory as revealed by mice with targeted disruption of the alpha2C-adrenoceptor gene. Eur J Neurosci 11(2):599-603. [PubMed: 10051760]  [MGI Ref ID J:53676]

Vanzelli AS; Medeiros A; Rolim N; Bartholomeu JB; Cunha TF; Bechara LR; Gomes ER; Mattos KC; Sirvente R; Salemi VM; Mady C; Negrao CE; Guatimosim S; Brum PC. 2013. Integrative effect of carvedilol and aerobic exercise training therapies on improving cardiac contractility and remodeling in heart failure mice. PLoS One 8(5):e62452. [PubMed: 23658728]  [MGI Ref ID J:202182]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2525.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $3283.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

    Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

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

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