In vitro assays - Oncodesign Services

Autoimmunity models

Circle Oncodesign Services

Preclinical CRO Services

for the Study of Autoimmune Diseases

 

Autoimmune diseases are triggered by dysregulated activation of immune cells, which can be linked to genetic causes. Rodent models of autoimmunity are helpful to decipher the disease triggering or sustaining mechanisms observed in patients.

Oncodesign Services offers CRO services for several preclinical models addressing a variety of autoimmune pathologies, and provides support for the de novo development of new autoimmune  models recently described in literature.

 

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Typical Autoimmunity Readouts

  • Clinical scoring
  • Body weight
  • Histopathology
  • Biomarker/drug monitoring
  • Gene expression in relevant tissues, by qPCR/dPCR

 

Autoimmunity Models

Industry-standard models are offered as well as new model development services:

  • Collagen-induced arthritis in mice (1)
  • Collagen-induced arthritis in rats (2)
  • Type-1 diabetes (T1D) in NOD mice (3)
  • Type-2 diabetes (T2D) in genetically obese leptin receptor-deficient mice (4)
  • Acute experimental autoimmune encephalomyelitis (EAE) / Multiple sclerosis (MS) model in mice, MOG35-55 peptide induced (5)
  • Remitting-relapsing experimental autoimmune encephalomyelitis (EAE) / Multiple sclerosis (MS) model in mice ,.PLP139-151 peptide induced (6)

Case Study

Rheumatoid arthritis preclinical rat model

Collagen-induced arthritis in rats is a model of chronic inflammatory synovitis that resembles human RA.  Genetically susceptible Lewis rats immunized intra-dermally with type II collagen emulsified in Freund’s incomplete adjuvant (prime & boost, 1 week apart) develop a polyarthritis within 10-14 days.

Autoimmunity - Collagen-induced arthritis score in rat
Body Weight Ratio collagen induced arthritis
  • References

    (1) Collagen-induced arthritis in mice

    • Review of models:

    Choudhary N, Bhatt LK, Prabhavalkar KS. Experimental animal models for rheumatoid arthritis. Immunopharmacol Immunotoxicol. 2018 Jun;40(3):193-200. doi: 10.1080/08923973.2018.1434793. Epub 2018 Feb 12. PMID: 29433367 : https://www.tandfonline.com/doi/abs/10.1080/08923973.2018.1434793?journalCode=iipi20

    • Papers explicating protocols:

    Brand DD, Latham KA, Rosloniec EF. Collagen-induced arthritis. Nat Protoc. 2007;2(5):1269-75. doi: 10.1038/nprot.2007.173. PMID: 17546023 : https://www.nature.com/articles/nprot.2007.173

    Miyoshi M, Liu S. Collagen-Induced Arthritis Models. Methods Mol Biol. 2018;1868:3-7. doi: 10.1007/978-1-4939-8802-0_1. PMID: 30244448 : https://link.springer.com/protocol/10.1007/978-1-4939-8802-0_1

    Bevaart L, Vervoordeldonk MJ, Tak PP. Collagen-induced arthritis in mice. Methods Mol Biol. 2010;602:181-92. doi: 10.1007/978-1-60761-058-8_11. PMID: 20012399 : https://link.springer.com/protocol/10.1007/978-1-60761-058-8_11

    • Demonstration of the efficacy of compounds:

    Zhang GB, Jia ZJ, Zhang MH, Li YJ, Tian LY, Cheng J. Flaccidoside II ameliorates collagen-induced arthritis in mice. Eur J Pharmacol. 2020 Aug 5;880:173155. doi: 10.1016/j.ejphar.2020.173155. Epub 2020 Apr 30. Erratum in: Eur J Pharmacol. 2021 Apr 15;897:173963. PMID: 32360348 : https://www.sciencedirect.com/science/article/abs/pii/S0014299920302478?via%3Dihub

    Liu H, Zhao J, Su M, Tian X, Lai L. Recombinant CD300c-Ig fusion protein attenuates collagen-induced arthritis in mice. Rheumatology (Oxford). 2022 Mar 2;61(3):1255-1264. doi: 10.1093/rheumatology/keab450. PMID: 34021311; PMCID: PMC8889306. : https://academic.oup.com/rheumatology/article-abstract/61/3/1255/6280557?redirectedFrom=fulltext&login=false       

    Li J, Sun Q, Zheng C, Bai C, Liu C, Zhao X, Deng P, Chai L, Jia Y. Lipoxin A4-Mediated p38 MAPK Signaling Pathway Protects Mice Against Collagen-Induced Arthritis. Biochem Genet. 2021 Feb;59(1):346-365. doi: 10.1007/s10528-020-10016-9. Epub 2020 Nov 22. PMID: 33221976. : https://link.springer.com/article/10.1007/s10528-020-10016-9

     

    (2) Collagen-induced arthritis in rats

    • Review of models:

    Choudhary N, Bhatt LK, Prabhavalkar KS. Experimental animal models for rheumatoid arthritis. Immunopharmacol Immunotoxicol. 2018 Jun;40(3):193-200. doi: 10.1080/08923973.2018.1434793. Epub 2018 Feb 12. PMID: 29433367 : https://www.tandfonline.com/doi/abs/10.1080/08923973.2018.1434793?journalCode=iipi20

    • Papers explaining protocols:

    Griffiths MM, Cannon GW, Corsi T, Reese V, Kunzler K. Collagen-induced arthritis in rats. Methods Mol Med. 2007;136:201-14. doi: 10.1007/978-1-59745-402-5_15. PMID: 17983150 : https://pubmed.ncbi.nlm.nih.gov/17983150/

    • Demonstration of the efficacy of compounds:

    Gao Q, Qin H, Zhu L, Li D, Hao X. Celastrol attenuates collagen-induced arthritis via inhibiting oxidative stress in rats. Int Immunopharmacol. 2020 Jul;84:106527. doi: 10.1016/j.intimp.2020.106527. Epub 2020 May 11. PMID: 32402948 : https://www.sciencedirect.com/science/article/pii/S1567576920305324?via%3Dihub

    Chen M, You G, Xie C, Yang R, Hu W, Zheng Z, Liu S, Ye L. Pharmacokinetics of metformin in collagen-induced arthritis rats. Biochem Pharmacol. 2021 Mar;185:114413. doi: 10.1016/j.bcp.2021.114413. Epub 2021 Jan 9. PMID: 33434538 : https://www.sciencedirect.com/science/article/abs/pii/S0006295221000095?via%3Dihub

    Ahmad Khan M, Sarwar AHMG, Rahat R, Ahmed RS, Umar S. Stigmasterol protects rats from collagen induced arthritis by inhibiting proinflammatory cytokines. Int Immunopharmacol. 2020 Aug;85:106642. doi: 10.1016/j.intimp.2020.106642. Epub 2020 May 26. PMID: 32470883. : https://www.sciencedirect.com/science/article/pii/S1567576920300254?via%3Dihub

     

    (3) Type-1 diabetes (T1D) in NOD mice

    • Review :

    Pearson JA, Wong FS, Wen L. The importance of the Non Obese Diabetic (NOD) mouse model in autoimmune diabetes. J Autoimmun. 2016 Jan;66:76-88. doi: 10.1016/j.jaut.2015.08.019. Epub 2015 Sep 26. PMID: 26403950; PMCID: PMC4765310 : https://www.sciencedirect.com/science/article/abs/pii/S0896841115300378?via%3Dihub

    • Role of food:

    Clark AL, Yan Z, Chen SX, Shi V, Kulkarni DH, Diwan A, Remedi MS. High-fat diet prevents the development of autoimmune diabetes in NOD mice. Diabetes Obes Metab. 2021 Nov;23(11):2455-2465. doi: 10.1111/dom.14486. Epub 2021 Aug 2. PMID: 34212475; PMCID: PMC8490276. https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.14486

    • Role of sex:

    Tur DA, Khotskin NV, Akulov AE. Sex difference feeding behaviour of NOD SCID mice in a pharmacological model of type 1 diabetes. J Anim Physiol Anim Nutr (Berl). 2021 Sep;105(5):984-988. doi: 10.1111/jpn.13517. Epub 2021 Mar 2. PMID: 33655640. https://onlinelibrary.wiley.com/doi/10.1111/jpn.13517

    • Insulin treatments:

    Martens PJ, Ellis D, Bruggeman Y, Viaene M, Laureys J, Teyton L, Mathieu C, Gysemans C. Preventing type 1 diabetes in late-stage pre-diabetic NOD mice with insulin: A central role for alum as adjuvant. Front Endocrinol (Lausanne). 2022 Oct 20;13:1023264. doi: 10.3389/fendo.2022.1023264. PMID: 36339431; PMCID: PMC9630573. https://www.frontiersin.org/articles/10.3389/fendo.2022.1023264/full

    • Testing of potential treatments:

    Li W, Zhang Y, Li R, Wang Y, Chen L, Dai S. A Novel Tolerogenic Antibody Targeting Disulfide-Modified Autoantigen Effectively Prevents Type 1 Diabetes in NOD Mice. Front Immunol. 2022 Aug 11;13:877022. doi: 10.3389/fimmu.2022.877022. PMID: 36032077; PMCID: PMC9406144. https://www.frontiersin.org/articles/10.3389/fimmu.2022.877022/full

    Wilson CS, Hoopes EM, Falk AC, Moore DJ. A human IgM enriched immunoglobulin preparation, Pentaglobin, reverses autoimmune diabetes without immune suppression in NOD mice. Sci Rep. 2022 Jul 11;12(1):11731. doi: 10.1038/s41598-022-15676-8. PMID: 35821261; PMCID: PMC9274958. https://www.nature.com/articles/s41598-022-15676-8

     

    (4) Type-2 diabetes (T2D) in genetically obese leptin receptor-deficient mice

    • Review:

    Wang B, Chandrasekera PC, Pippin JJ. Leptin- and leptin receptor-deficient rodent models: relevance for human type 2 diabetes. Curr Diabetes Rev. 2014 Mar;10(2):131-45. doi: 10.2174/1573399810666140508121012. PMID: 24809394; PMCID: PMC4082168. http://www.eurekaselect.com/article/60417

    Suriano F, Vieira-Silva S, Falony G, Roumain M, Paquot A, Pelicaen R, Régnier M, Delzenne NM, Raes J, Muccioli GG, Van Hul M, Cani PD. Novel insights into the genetically obese (ob/ob) and diabetic (db/db) mice: two sides of the same coin. Microbiome. 2021 Jun 28;9(1):147. doi: 10.1186/s40168-021-01097-8. PMID: 34183063; PMCID: PMC8240277. https://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-021-01097-8

    • Stress involvement:

    Razzoli M, McCallum J, Gurney A, Engeland WC, Bartolomucci A. Chronic stress aggravates glucose intolerance in leptin receptor-deficient (db/db) mice. Genes Nutr. 2015 May;10(3):458. doi: 10.1007/s12263-015-0458-2. Epub 2015 Mar 20. PMID: 25791744; PMCID: PMC4366428. https://link.springer.com/article/10.1007/s12263-015-0458-2

    Wang Y, Dilidaxi D, Wu Y, Sailike J, Sun X, Nabi XH. Composite probiotics alleviate type 2 diabetes by regulating intestinal microbiota and inducing GLP-1 secretion in db/db mice. Biomed Pharmacother. 2020 May;125:109914. doi: 10.1016/j.biopha.2020.109914. Epub 2020 Feb 5. PMID: 32035395. https://www.sciencedirect.com/science/article/pii/S0753332220301049?via%3Dihub

    • Treatment testing:

    Wang M, Song L, Strange C, Dong X, Wang H. Therapeutic Effects of Adipose Stem Cells from Diabetic Mice for the Treatment of Type 2 Diabetes. Mol Ther. 2018 Aug 1;26(8):1921-1930. doi: 10.1016/j.ymthe.2018.06.013. Epub 2018 Jun 19. PMID: 30005867; PMCID: PMC6094391. https://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/

    Wang Y, Dilidaxi D, Wu Y, Sailike J, Sun X, Nabi XH. Composite probiotics alleviate type 2 diabetes by regulating intestinal microbiota and inducing GLP-1 secretion in db/db mice. Biomed Pharmacother. 2020 May;125:109914. doi: 10.1016/j.biopha.2020.109914. Epub 2020 Feb 5. PMID: 32035395. https://www.sciencedirect.com/science/article/pii/S0753332220301049?via%3Dihub

    Jiang Y, Xie F, Lv X, Wang S, Liao X, Yu Y, Dai Q, Zhang Y, Meng J, Hu G, Peng Z, Tao L. Mefunidone ameliorates diabetic kidney disease in STZ and db/db mice. FASEB J. 2021 Jan;35(1):e21198. doi: 10.1096/fj.202001138RR. Epub 2020 Nov 22. PMID: 33225469.  https://faseb.onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202001138RR

    Han X, Tao Y, Deng Y, Yu J, Sun Y, Jiang G. Metformin accelerates wound healing in type 2 diabetic db/db mice. Mol Med Rep. 2017 Dec;16(6):8691-8698. doi: 10.3892/mmr.2017.7707. Epub 2017 Oct 4. PMID: 28990070; PMCID: PMC5779947. https://www.spandidos-publications.com/mmr/16/6/8691

     

    (5) Acute experimental autoimmune encephalomyelitis (EAE) / Multiple sclerosis (MS) model in mice, MOG35-55 peptide induced

    • Methods:

    Bittner S, Afzali AM, Wiendl H, Meuth SG. Myelin oligodendrocyte glycoprotein (MOG35-55) induced experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. J Vis Exp. 2014 Apr 15;(86):51275. doi: 10.3791/51275. PMID: 24797125; PMCID: PMC4172026. https://www.jove.com/t/51275/myelin-oligodendrocyte-glycoprotein-mog35–55-induced-experimental-autoimmune-encephalomyelitis-eae-in-c57bl/6-mice    

    Aharoni R, Globerman R, Eilam R, Brenner O, Arnon R. Titration of myelin oligodendrocyte glycoprotein (MOG) – Induced experimental autoimmune encephalomyelitis (EAE) model. J Neurosci Methods. 2021 Mar 1;351:108999. doi: 10.1016/j.jneumeth.2020.108999. Epub 2020 Nov 12. PMID: 33189793. https://www.sciencedirect.com/science/article/abs/pii/S0165027020304222?via%3Dihub

    • Role of immune system:

    Weber MS, Prod’homme T, Patarroyo JC, Molnarfi N, Karnezis T, Lehmann-Horn K, Danilenko DM, Eastham-Anderson J, Slavin AJ, Linington C, Bernard CC, Martin F, Zamvil SS. B-cell activation influences T-cell polarization and outcome of anti-CD20 B-cell depletion in central nervous system autoimmunity. Ann Neurol. 2010 Sep;68(3):369-83. doi: 10.1002/ana.22081. PMID: 20641064; PMCID: PMC3375897. https://onlinelibrary.wiley.com/doi/10.1002/ana.22081

    Aulova KS, Urusov AA, Sedykh SE, Toporkova LB, Lopatnikova JA, Buneva VN, Sennikov SV, Budde T, Meuth SG, Popova NA, Orlovskaya IA, Nevinsky GA. The association between EAE development in mice and the production of autoantibodies and abzymes after immunization of mice with different antigens. J Cell Mol Med. 2021 Mar;25(5):2493-2504. doi: 10.1111/jcmm.16183. Epub 2021 Feb 9. PMID: 33560578; PMCID: PMC7933958. https://onlinelibrary.wiley.com/doi/10.1111/jcmm.16183                                                                                        

    Ruppova K, Lim JH, Fodelianaki G, August A, Neuwirth A. Eosinophils are dispensable for development of MOG35-55-induced experimental autoimmune encephalomyelitis in mice. Immunol Lett. 2021 Nov;239:72-76. doi: 10.1016/j.imlet.2021.09.001. Epub 2021 Sep 6. PMID: 34499922. https://www.sciencedirect.com/science/article/abs/pii/S0165247821001425?via%3Dihub

    • Treatment testing:

    Remlinger J, Madarasz A, Guse K, Hoepner R, Bagnoud M, Meli I, Feil M, Abegg M, Linington C, Shock A, Boroojerdi B, Kiessling P, Smith B, Enzmann V, Chan A, Salmen A. Antineonatal Fc Receptor Antibody Treatment Ameliorates MOG-IgG-Associated Experimental Autoimmune Encephalomyelitis. Neurol Neuroimmunol Neuroinflamm. 2022 Jan 13;9(2):e1134. doi: 10.1212/NXI.0000000000001134. PMID: 35027475; PMCID: PMC8759074. https://nn.neurology.org/content/9/2/e1134.long

     

    (6) Remitting-relapsing experimental autoimmune encephalomyelitis (EAE) / Multiple sclerosis (MS) model in mice, PLP139-151 peptide induced

    • Methods :

    Laaker C, Hsu M, Fabry Z, Miller SD, Karpus WJ. Experimental Autoimmune Encephalomyelitis in the Mouse. Curr Protoc. 2021 Dec;1(12):e300. doi: 10.1002/cpz1.300. Erratum in: Curr Protoc. 2022 Aug;2(8):e554. PMID: 34870897. https://currentprotocols.onlinelibrary.wiley.com/doi/10.1002/cpz1.300

    • Involvement of the immune system:

    Pascual DW, Ochoa-Repáraz J, Rynda A, Yang X. Tolerance in the absence of autoantigen. Endocr Metab Immune Disord Drug Targets. 2007 Sep;7(3):203-10. doi: 10.2174/187153007781662549. PMID: 17897047; PMCID: PMC9811400. https://www.eurekaselect.com/article/23708

    • Role of exercise:

    Fainstein N, Tyk R, Touloumi O, Lagoudaki R, Goldberg Y, Agranyoni O, Navon-Venezia S, Katz A, Grigoriadis N, Ben-Hur T, Einstein O. Exercise intensity-dependent immunomodulatory effects on encephalomyelitis. Ann Clin Transl Neurol. 2019 Sep;6(9):1647-1658. doi: 10.1002/acn3.50859. Epub 2019 Aug 1. PMID: 31368247; PMCID: PMC6764499. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764499/

    Shahi SK, Ghimire S, Lehman P, Mangalam AK. Obesity induced gut dysbiosis contributes to disease severity in an animal model of multiple sclerosis. Front Immunol. 2022 Sep 9;13:966417. doi: 10.3389/fimmu.2022.966417. PMID: 36164343; PMCID: PMC9509138. https://www.frontiersin.org/articles/10.3389/fimmu.2022.966417/full

    • Testing of treatments:

    Fagone P, Mangano K, Quattrocchi C, Motterlini R, Di Marco R, Magro G, Penacho N, Romao CC, Nicoletti F. Prevention of clinical and histological signs of proteolipid protein (PLP)-induced experimental allergic encephalomyelitis (EAE) in mice by the water-soluble carbon monoxide-releasing molecule (CORM)-A1. Clin Exp Immunol. 2011 Mar;163(3):368-74. doi: 10.1111/j.1365-2249.2010.04303.x. Epub 2011 Jan 14. PMID: 21235533; PMCID: PMC3048621. https://academic.oup.com/cei/article/163/3/368/6428930?login=false

    Al-Mazroua HA, Nadeem A, Ansari MA, Attia SM, Bakheet SA, Albekairi TH, Ali N, Alasmari F, Algahtani M, Alsaad AMS, Ahmad SF. CCR1 antagonist ameliorates experimental autoimmune encephalomyelitis by inhibition of Th9/Th22-related markers in the brain and periphery. Mol Immunol. 2022 Apr;144:127-137. doi: 10.1016/j.molimm.2022.02.017. Epub 2022 Feb 24. PMID: 35219910 https://www.sciencedirect.com/science/article/abs/pii/S0161589022000463?via%3Dihub

    Legge KL, Bell JJ, Li L, Gregg R, Caprio JC, Zaghouani H. Multi-modal antigen specific therapy for autoimmunity. Int Rev Immunol. 2001 Oct;20(5):593-611. doi: 10.3109/08830180109045580. PMID: 11890614

     https://www.tandfonline.com/doi/abs/10.3109/08830180109045580