Strain Name:

B6.129S1-Nt5etm1Lft/J

Stock Number:

018986

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Availability:

Repository- Live

These mice may be useful when studying CD73-generated adenosine receptor signaling and antitumor immune responses.

Description

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.
Mating SystemHomozygote x Homozygote         (Female x Male)   25-MAR-13
Specieslaboratory mouse
GenerationN14+N1F4 (26-NOV-12)
Generation Definitions
 
Donating Investigator Linda F. Thompson,   Oklahoma Medical Research Foundation

Description
A neo cassette replaces exon 3 of the ecto-5' nucleotidase (Nt5e) gene, abolishing CD73 enzyme activity. A shorter transcript is produced at about 10% of WT levels, but no functional protein is detectable. Nt5e encodes Cd73, a membrane-bound glycoprotein expressed on many cell types including subsets of T and B lymphocytes including regulator T cell (Tregs), endothelial cells, and mesenchymal cells. CD73 can hydrolyze nucleoside monophosphates, such as AMP, into bioactive intermediates like adenosine. CD73-generated adenosine activates transmembrane adenosine receptors and can act as either a pro- or anti-inflammatory mediator. Adenosine also regulates endothelial permeability, platelet activation, leukocyte adhesion, and lymphocyte migration into draining lymph nodes after an inflammatory stimulus. CD73-dependent adenosine receptor signaling protects mice during renal ischemia and inhibits vascular leakage during hypoxia. CD73 inhibits antitumor immune responses and is tolerogenic for cardiac and airway allografts. Homozygous CD73-/- mice are viable and fertile. Under hypoxic conditions, these CD73-deficient mice exhibit increased vascular leakage and display increased edema in all organs except the brain. CD73 deficient mice are protected from experimental autoimmune encephalomyelitis (EAE). The severity of graft-vs-host disease (GVHD) is increased in these mice, as are anti-tumor immune responses.

Development
A targeting vector was designed to replace exon 3 of the ecto-5' nucleotidase, (Nt5e) gene with a neomycin resistance (neo) cassette in reverse orientation to the gene. The construct was electroporated into 129S1/Sv-Oca2+ Tyr+ Kitl+-derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric female was bred to a C57BL/6J male. The resulting heterozygous mice were crossed and their homozygous offspring were backcrossed to C57BL/6J mice for at least 14 generations (see SNP results below) prior to sending males to The Jackson Laboratory Repository in 2012. Upon arrival, males were used to cryopreserve sperm. To establish the living mouse colony, an aliquot of the frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the first generation rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 3 of the 5 markers that determine C57BL/6J from C57BL/6N were found to be heterozygous in all mice tested. These data show that the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6N and C57BL/6J genetic background.

Control Information

  Control
   000664 C57BL/6J (approximate)
   005304 C57BL/6NJ (approximate)
 
  Considerations for Choosing Controls

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.
Calcification of Joints and Arteries; CALJA   (NT5E)
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.

Nt5etm1Lft/Nt5etm1Lft

        involves: 129S1/Sv * C57BL/6
  • behavior/neurological phenotype
  • increased aggression toward humans
    • under hypoxic conditions mutants are less compliant compared to wild-type littermates   (MGI Ref ID J:94697)
  • lethargy
    • under hypoxic conditions mutants are more lethargic compared to wild-type littermates   (MGI Ref ID J:94697)
  • cardiovascular system phenotype
  • altered response to myocardial infarction
    • ischemic preconditioning fails to attenuate infarct size as in wild-type mice   (MGI Ref ID J:131444)
    • however, treatment of mice with adenosine or 5' nucleotidase infusion partially-restores cardioprotection offered by ischemic preconditioning   (MGI Ref ID J:131444)
    • increased myocardial infarction size
      • mice exhibit increased infarct size after 60 minutes of ischemia compared to in similarly-treated wild-type mice   (MGI Ref ID J:131444)
  • increased vascular permeability
    • under hypoxic conditions increased vascular leakage is seen   (MGI Ref ID J:94697)
    • under normoxic conditions increased vascular permeability is seen in the lung and colon   (MGI Ref ID J:94697)
  • homeostasis/metabolism phenotype
  • abnormal response/metabolism to endogenous compounds
    • mice exhibit an attenuated bradycardia response to AMP   (MGI Ref ID J:131444)
  • altered response to myocardial infarction
    • ischemic preconditioning fails to attenuate infarct size as in wild-type mice   (MGI Ref ID J:131444)
    • however, treatment of mice with adenosine or 5' nucleotidase infusion partially-restores cardioprotection offered by ischemic preconditioning   (MGI Ref ID J:131444)
    • increased myocardial infarction size
      • mice exhibit increased infarct size after 60 minutes of ischemia compared to in similarly-treated wild-type mice   (MGI Ref ID J:131444)
  • edema
    • under hypoxic conditions increased edema is seen in all organs except the brain   (MGI Ref ID J:94697)
View Research Applications

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

Cancer Research
Tumor Resistance
Tumor Suppressor Genes

Cardiovascular Research
Vascular Defects
      platelet defect

Immunology, Inflammation and Autoimmunity Research
Graft vs. Host Disease
Inflammation

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Nt5etm1Lft
Allele Name targeted mutation 1, Linda F Thompson
Allele Type Targeted (Null/Knockout)
Common Name(s) Cd73-;
Mutation Made By Linda Thompson,   Oklahoma Medical Research Foundation
Strain of Origin129S1/Sv-Oca2<+> Tyr<+> Kitl<+>
Gene Symbol and Name Nt5e, 5' nucleotidase, ecto
Chromosome 9
Gene Common Name(s) 2210401F01Rik; 5' nucleotidase; AI447961; CALJA; CD73; E5NT; NT; NT5; NTE; Nt5; RIKEN cDNA 2210401F01 gene; eN; eNT; ecto-5'-nucleotidase; expressed sequence AI447961;
Molecular Note Exon 3 was replaced with a neo cassette in reverse orientation to transcription. Northern blot of kidneys from mutant animlas indicated a lack of transcript. [MGI Ref ID J:94697]

Genotyping

Genotyping Information

Genotyping Protocols

Nt5etm1Lft,

Separated MCA


Nt5etm1Lft, Separated PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Thompson LF; Eltzschig HK; Ibla JC; Van De Wiele CJ; Resta R; Morote-Garcia JC; Colgan SP. 2004. Crucial role for ecto-5'-nucleotidase (CD73) in vascular leakage during hypoxia. J Exp Med 200(11):1395-405. [PubMed: 15583013]  [MGI Ref ID J:94697]

Additional References

Nt5etm1Lft related

Alam MS; Kuo JL; Ernst PB; Derr-Castillo V; Pereira M; Gaines D; Costales M; Bigley E; Williams K. 2014. Ecto-5'-nucleotidase (CD73) regulates host inflammatory responses and exacerbates murine salmonellosis. Sci Rep 4:4486. [PubMed: 24670982]  [MGI Ref ID J:210462]

Algars A; Karikoski M; Yegutkin GG; Stoitzner P; Niemela J; Salmi M; Jalkanen S. 2011. Different role of CD73 in leukocyte trafficking via blood and lymph vessels. Blood 117(16):4387-93. [PubMed: 21346249]  [MGI Ref ID J:172831]

Dando R; Dvoryanchikov G; Pereira E; Chaudhari N; Roper SD. 2012. Adenosine Enhances Sweet Taste through A2B Receptors in the Taste Bud. J Neurosci 32(1):322-30. [PubMed: 22219293]  [MGI Ref ID J:179362]

Eckle T; Fullbier L; Wehrmann M; Khoury J; Mittelbronn M; Ibla J; Rosenberger P; Eltzschig HK. 2007. Identification of ectonucleotidases CD39 and CD73 in innate protection during acute lung injury. J Immunol 178(12):8127-37. [PubMed: 17548651]  [MGI Ref ID J:148575]

Eckle T; Krahn T; Grenz A; Kohler D; Mittelbronn M; Ledent C; Jacobson MA; Osswald H; Thompson LF; Unertl K; Eltzschig HK. 2007. Cardioprotection by ecto-5'-nucleotidase (CD73) and A2B adenosine receptors. Circulation 115(12):1581-90. [PubMed: 17353435]  [MGI Ref ID J:131444]

Ehrentraut H; Clambey ET; McNamee EN; Brodsky KS; Ehrentraut SF; Poth JM; Riegel AK; Westrich JA; Colgan SP; Eltzschig HK. 2013. CD73+ regulatory T cells contribute to adenosine-mediated resolution of acute lung injury. FASEB J 27(6):2207-19. [PubMed: 23413361]  [MGI Ref ID J:199964]

Eltzschig HK; Thompson LF; Karhausen J; Cotta RJ; Ibla JC; Robson SC; Colgan SP. 2004. Endogenous adenosine produced during hypoxia attenuates neutrophil accumulation: coordination by extracellular nucleotide metabolism. Blood 104(13):3986-92. [PubMed: 15319286]  [MGI Ref ID J:179876]

Ena SL; De Backer JF; Schiffmann SN; de Kerchove d'Exaerde A. 2013. FACS array profiling identifies Ecto-5' nucleotidase as a striatopallidal neuron-specific gene involved in striatal-dependent learning. J Neurosci 33(20):8794-809. [PubMed: 23678122]  [MGI Ref ID J:198421]

Fernandez P; Perez-Aso M; Smith G; Wilder T; Trzaska S; Chiriboga L; Franks A Jr; Robson SC; Cronstein BN; Chan ES. 2013. Extracellular generation of adenosine by the ectonucleotidases CD39 and CD73 promotes dermal fibrosis. Am J Pathol 183(6):1740-6. [PubMed: 24266925]  [MGI Ref ID J:207936]

Hart ML; Grenz A; Gorzolla IC; Schittenhelm J; Dalton JH; Eltzschig HK. 2011. Hypoxia-Inducible Factor-1{alpha}-Dependent Protection from Intestinal Ischemia/Reperfusion Injury Involves Ecto-5'-Nucleotidase (CD73) and the A2B Adenosine Receptor. J Immunol 186(7):4367-74. [PubMed: 21357264]  [MGI Ref ID J:170696]

Hart ML; Henn M; Kohler D; Kloor D; Mittelbronn M; Gorzolla IC; Stahl GL; Eltzschig HK. 2008. Role of extracellular nucleotide phosphohydrolysis in intestinal ischemia-reperfusion injury. FASEB J 22(8):2784-97. [PubMed: 18353866]  [MGI Ref ID J:137973]

Hart ML; Much C; Gorzolla IC; Schittenhelm J; Kloor D; Stahl GL; Eltzschig HK. 2008. Extracellular adenosine production by ecto-5'-nucleotidase protects during murine hepatic ischemic preconditioning. Gastroenterology 135(5):1739-1750.e3. [PubMed: 18804111]  [MGI Ref ID J:145638]

Hasegawa T; Bouis D; Liao H; Visovatti SH; Pinsky DJ. 2008. Ecto-5' nucleotidase (CD73)-mediated adenosine generation and signaling in murine cardiac allograft vasculopathy. Circ Res 103(12):1410-21. [PubMed: 19008478]  [MGI Ref ID J:155264]

Hasko G; Csoka B; Koscso B; Chandra R; Pacher P; Thompson LF; Deitch EA; Spolarics Z; Virag L; Gergely P; Rolandelli RH; Nemeth ZH. 2011. Ecto-5'-nucleotidase (CD73) decreases mortality and organ injury in sepsis. J Immunol 187(8):4256-67. [PubMed: 21918191]  [MGI Ref ID J:179308]

Kiss J; Yegutkin GG; Koskinen K; Savunen T; Jalkanen S; Salmi M. 2007. IFN-beta protects from vascular leakage via up-regulation of CD73. Eur J Immunol 37(12):3334-8. [PubMed: 18034430]  [MGI Ref ID J:128495]

Kulesskaya N; Voikar V; Peltola M; Yegutkin GG; Salmi M; Jalkanen S; Rauvala H. 2013. CD73 is a major regulator of adenosinergic signalling in mouse brain. PLoS One 8(6):e66896. [PubMed: 23776700]  [MGI Ref ID J:204222]

Louis NA; Robinson AM; Macmanus CF; Karhausen J; Scully M; Colgan SP. 2008. Control of IFN-{alpha}A by CD73: Implications for Mucosal Inflammation. J Immunol 180(6):4246-55. [PubMed: 18322237]  [MGI Ref ID J:132954]

Mahamed DA; Mills JH; Egan CE; Denkers EY; Bynoe MS. 2012. CD73-generated adenosine facilitates Toxoplasma gondii differentiation to long-lived tissue cysts in the central nervous system. Proc Natl Acad Sci U S A 109(40):16312-7. [PubMed: 22988118]  [MGI Ref ID J:190107]

Methner C; Schmidt K; Cohen MV; Downey JM; Krieg T. 2010. Both A2a and A2b adenosine receptors at reperfusion are necessary to reduce infarct size in mouse hearts. Am J Physiol Heart Circ Physiol :. [PubMed: 20709859]  [MGI Ref ID J:163831]

Mills JH; Thompson LF; Mueller C; Waickman AT; Jalkanen S; Niemela J; Airas L; Bynoe MS. 2008. CD73 is required for efficient entry of lymphocytes into the central nervous system during experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 105(27):9325-30. [PubMed: 18591671]  [MGI Ref ID J:138192]

Ohtsuka T; Changelian PS; Bouis D; Noon K; Harada H; Lama VN; Pinsky DJ. 2010. Ecto-5'-nucleotidase (CD73) attenuates allograft airway rejection through adenosine 2A receptor stimulation. J Immunol 185(2):1321-9. [PubMed: 20548026]  [MGI Ref ID J:162920]

Peng Z; Borea PA; Wilder T; Yee H; Chiriboga L; Blackburn MR; Azzena G; Resta G; Cronstein BN. 2009. Adenosine signaling contributes to ethanol-induced fatty liver in mice. J Clin Invest 119(3):582-94. [PubMed: 19221436]  [MGI Ref ID J:146795]

Petrovic-Djergovic D; Hyman MC; Ray JJ; Bouis D; Visovatti SH; Hayasaki T; Pinsky DJ. 2012. Tissue-resident ecto-5' nucleotidase (CD73) regulates leukocyte trafficking in the ischemic brain. J Immunol 188(5):2387-98. [PubMed: 22291183]  [MGI Ref ID J:181359]

Regateiro FS; Howie D; Nolan KF; Agorogiannis EI; Greaves DR; Cobbold SP; Waldmann H. 2011. Generation of anti-inflammatory adenosine byleukocytes is regulated by TGF-beta. Eur J Immunol 41(10):2955-65. [PubMed: 21770045]  [MGI Ref ID J:176801]

Reutershan J; Vollmer I; Stark S; Wagner R; Ngamsri KC; Eltzschig HK. 2009. Adenosine and inflammation: CD39 and CD73 are critical mediators in LPS-induced PMN trafficking into the lungs. FASEB J 23(2):473-82. [PubMed: 18838482]  [MGI Ref ID J:146027]

Sowa NA; Taylor-Blake B; Zylka MJ. 2010. Ecto-5'-nucleotidase (CD73) inhibits nociception by hydrolyzing AMP to adenosine in nociceptive circuits. J Neurosci 30(6):2235-44. [PubMed: 20147550]  [MGI Ref ID J:157843]

Stagg J; Beavis PA; Divisekera U; Liu MC; Moller A; Darcy PK; Smyth MJ. 2012. CD73-deficient mice are resistant to carcinogenesis. Cancer Res 72(9):2190-6. [PubMed: 22396496]  [MGI Ref ID J:185750]

Stagg J; Divisekera U; Duret H; Sparwasser T; Teng MW; Darcy PK; Smyth MJ. 2011. CD73-Deficient Mice Have Increased Antitumor Immunity and Are Resistant to Experimental Metastasis. Cancer Res 71(8):2892-2900. [PubMed: 21292811]  [MGI Ref ID J:171004]

Street SE; Kramer NJ; Walsh PL; Taylor-Blake B; Yadav MC; King IF; Vihko P; Wightman RM; Millan JL; Zylka MJ. 2013. Tissue-nonspecific alkaline phosphatase acts redundantly with PAP and NT5E to generate adenosine in the dorsal spinal cord. J Neurosci 33(27):11314-22. [PubMed: 23825434]  [MGI Ref ID J:199822]

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]

Tsukamoto H; Chernogorova P; Ayata K; Gerlach UV; Rughani A; Ritchey JW; Ganesan J; Follo M; Zeiser R; Thompson LF; Idzko M. 2012. Deficiency of CD73/ecto-5'-nucleotidase in mice enhances acute graft-versus-host disease. Blood 119(19):4554-64. [PubMed: 22262774]  [MGI Ref ID J:185014]

Volmer JB; Thompson LF; Blackburn MR. 2006. Ecto-5'-nucleotidase (CD73)-mediated adenosine production is tissue protective in a model of bleomycin-induced lung injury. J Immunol 176(7):4449-58. [PubMed: 16547283]  [MGI Ref ID J:129862]

Wang L; Fan J; Chen S; Zhang Y; Curiel TJ; Zhang B. 2013. Graft-versus-host disease is enhanced by selective CD73 blockade in mice. PLoS One 8(3):e58397. [PubMed: 23520507]  [MGI Ref ID J:199912]

Wang L; Fan J; Thompson LF; Zhang Y; Shin T; Curiel TJ; Zhang B. 2011. CD73 has distinct roles in nonhematopoietic and hematopoietic cells to promote tumor growth in mice. J Clin Invest 121(6):2371-82. [PubMed: 21537079]  [MGI Ref ID J:173922]

Weissmuller T; Campbell EL; Rosenberger P; Scully M; Beck PL; Furuta GT; Colgan SP. 2008. PMNs facilitate translocation of platelets across human and mouse epithelium and together alter fluid homeostasis via epithelial cell-expressed ecto-NTPDases. J Clin Invest 118(11):3682-92. [PubMed: 18924612]  [MGI Ref ID J:144579]

Yegutkin GG; Hytonen J; Samburski SS; Yrjanainen H; Jalkanen S; Viljanen MK. 2010. Disordered lymphoid purine metabolism contributes to the pathogenesis of persistent Borrelia garinii infection in mice. J Immunol 184(9):5112-20. [PubMed: 20357256]  [MGI Ref ID J:160455]

Yegutkin GG; Marttila-Ichihara F; Karikoski M; Niemela J; Laurila JP; Elima K; Jalkanen S; Salmi M. 2011. Altered purinergic signaling in CD73-deficient mice inhibits tumor progression. Eur J Immunol 41(5):1231-41. [PubMed: 21469131]  [MGI Ref ID J:175403]

Zhang D; Xiong W; Chu S; Sun C; Albensi BC; Parkinson FE. 2012. Inhibition of hippocampal synaptic activity by ATP, hypoxia or oxygen-glucose deprivation does not require CD73. PLoS One 7(6):e39772. [PubMed: 22761898]  [MGI Ref ID J:187915]

Zielinski MR; Taishi P; Clinton JM; Krueger JM. 2012. 5'-Ectonucleotidase-knockout mice lack non-REM sleep responses to sleep deprivation. Eur J Neurosci 35(11):1789-98. [PubMed: 22540145]  [MGI Ref ID J:207668]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX18

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice may be bred together.
Mating SystemHomozygote x Homozygote         (Female x Male)   25-MAR-13
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


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

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $199.90Female or MaleHomozygous for Nt5etm1Lft  
Price per Pair (US dollars $)Pair Genotype
$399.80Homozygous for Nt5etm1Lft x Homozygous for Nt5etm1Lft  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $259.90Female or MaleHomozygous for Nt5etm1Lft  
Price per Pair (US dollars $)Pair Genotype
$519.80Homozygous for Nt5etm1Lft x Homozygous for Nt5etm1Lft  

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Repository-Live.
Repository-Live represents an exclusive set of over 1800 unique mouse models across a vast array of research areas. Breeding colonies provide mice for large and small orders and fluctuate in size depending on current research demand. If a strain is not immediately available, you will receive an estimated availability timeframe for your inquiry or order in 2-3 business days. Repository strains typically are delivered at 4 to 8 weeks of age. Requests for specific ages will be noted but not guaranteed and we do not accept age requests for breeder pairs. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, we will do our best to accommodate your age request.

Control Information

  Control
   000664 C57BL/6J (approximate)
   005304 C57BL/6NJ (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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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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