Skip to main content

Advertisement

Log in

Challenges and opportunities in animal models of psoriatic arthritis

  • Review
  • Published:
Inflammation Research Aims and scope Submit manuscript

Abstract

Objective

To review the preparation, characteristics and research progress of different PsA animal models.

Methods

Computerized searches were conducted in CNKI, PubMed and other databases to classify and discuss the relevant studies on PsA animal models. The search keywords were “PsA and animal model(s), PsA and animal(s), PsA and mouse, PsA and mice, PsA and rat(s), PsA and rabbit(s), PsA and dog(s)”

Results

The experimental animals currently used to study PsA are mainly rodents, including mice and rats. According to the different methods of preparing the models, the retrieved animal models were classified into spontaneous or genetic mutation, transgenic and induced animal models. These PsA animal models involve multiple pathogenesis, some experimental animals’ lesions appear in a short and comprehensive cycle, some have a high success rate in molding, and some are complex and less reproducibility. This article summarizes the preparation methods, advantages and disadvantages of different models.

Conclusions

The animal models of PsA aim to mimic the clinicopathological alterations of PsA patients through gene mutation, transgenesis or targeted proinflammatory factor and to reveal new pathogenic pathways and therapeutic targets by exploring the pathological features and clinical manifestations of the disease. This work will have very far-reaching implications for the in-depth understanding of PsA and the development of new drugs.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

Data availability

All data included in this study are available upon request by contact with the corresponding author.

Abbreviations

PsA:

Psoriatic arthritis

PsO:

Psoriasis

AE:

Ankylosing enthesitis

SpA:

Spondyloarthritis

ANKENT:

Ankylosing enthesopathy

RA:

Rheumatoid arthritis

CV:

Conventional

GF:

Germ-free

2m:

Human β2 micro-globulin

SPF:

Specific pathogen-free

MIP:

Mannan-induced PsO and PsA

mCAIA:

Mannan-enhanced collagen antibody-induced arthritis

MHC:

The major histocompatibility complex

EGF:

Epidermal growth factor

TGF-β:

Transforming growth factor β

SOCS3:

Suppressor of cytokine signaling 3

STAT3:

Signal transducer and activator of transcription 3

CIA:

Collagen-induced arthritis

ROS:

Reactive oxygen species

NOS2:

Nitric oxide synthase 2

FLS:

Synovial fibroblasts

EEV:

Enhanced episomal vector

PBMC:

Peripheral blood mononuclear cell

References

  1. Veale DJ, Fearon U. The pathogenesis of psoriatic arthritis. Lancet. 2018;391(10136):2273–84. https://doi.org/10.1016/S0140-6736(18)30830-4.

    Article  CAS  PubMed  Google Scholar 

  2. Ridley LJ, Han J, Ridley WE, Xiang H. Mouse ear erosions: psoriatic arthritis. J Med Imaging Radiat Oncol. 2018;62(Suppl 1):145. https://doi.org/10.1111/1754-9485.20_12786.

    Article  PubMed  Google Scholar 

  3. Meng JH, Zhao HT, Chen HY. Research progress of pathogenesis in psoriatic arthritis. Chin J Immunol. 2021;37(1):119–23. https://doi.org/10.3969/j.issn.1000-484X,2021.01.023.(inchinese).

    Article  Google Scholar 

  4. Hackett S, Ogdie A, Coates LC. Psoriatic arthritis: prospects for the future. Ther Adv Musculoskelet Dis. 2022;14:1759720X221086710. https://doi.org/10.1177/1759720X2210. (86710).

    Article  PubMed  PubMed Central  Google Scholar 

  5. Ocampo DV, Gladman D. Psoriatic arthritis. F1000Res. 2019. https://doi.org/10.12688/f1000research.19144.1. (8:F1000 Faculty Rev-1665).

    Article  PubMed Central  Google Scholar 

  6. Umezawa Y. Psoriatic arthritis. J Dermatol. 2021;48(6):741–9. https://doi.org/10.1111/1346-8138.15954.

    Article  PubMed  Google Scholar 

  7. Boehncke WH. Psoriasis and psoriatic arthritis: flip sides of the coin? Acta Derm Venereol. 2016;96(4):436–41. https://doi.org/10.2340/00015555-2385.

    Article  CAS  PubMed  Google Scholar 

  8. Lu CF, Leng XM. Susceptibility genes of psoriatic arthritis. Chin J Allergy Clin Immunol. 2020;14(03):272–8. https://doi.org/10.3969/j.issn.1673-8705.2020.03.018 (in Chinese)

    Article  Google Scholar 

  9. Gao J, Su Y, Wang C. Diagnosis and treatment standards for psoriasis arthritis. In: Zhao Y, Zeng X, editors. Diagnostic and treatment standards for rheumatology. Beijing: People’s Medical Publishing House; 2022. p. 20–30 (in Chinese).

    Google Scholar 

  10. Nunn CL, Rothschild B, Gittleman JL. Why are some species more commonly afflicted by arthritis than others? A comparative study of spondyloarthropathy in primates and carnivores. J Evol Biol. 2007;20(2):460–70. https://doi.org/10.1111/j.1420-9101.2006.01276.x.

    Article  CAS  PubMed  Google Scholar 

  11. Choudhary N, Bhatt LK, Prabhavalkar KS. Experimental animal models for rheumatoid arthritis. Immunopharmacol Immunotoxicol. 2018;40(3):193–200. https://doi.org/10.1080/08923973.2018.1434793.

    Article  CAS  PubMed  Google Scholar 

  12. Braem K, Carter S, Lories RJ. Spontaneous arthritis and ankylosis in male DBA/1 mice: further evidence for a role of behavioral factors in “stress-induced arthritis.” Biol Proc Online. 2012;14(1):10. https://doi.org/10.1186/1480-9222-14-10.

    Article  Google Scholar 

  13. Weinreich S, Eulderink F, Capkova J, Pla M, Gaede K, Heesemann J, et al. HLA-B27 as a relative risk factor in ankylosing enthesopathy in transgenic mice. Hum Immunol. 1995;42(2):103–15. https://doi.org/10.1016/0198-8859(94)00034-n.

    Article  CAS  PubMed  Google Scholar 

  14. Eulderink F, Ivanyi P, Weinreich S. Histopathology of murine ankylosing enthesopathy. Pathol Res Pract. 1998;194(11):797–803. https://doi.org/10.1016/S0344-0338(98)80070-8.

    Article  CAS  PubMed  Google Scholar 

  15. Sinkorová Z, Capková J, Niederlová J, Stepánková R, Sinkora J. Commensal intestinal bacterial strains trigger ankylosing enthesopathy of the ankle in inbred B10.BR (H-2(k)) male mice. Hum Immunol. 2008;69(12):845–50. https://doi.org/10.1016/j.humimm.2008.08.296.

    Article  CAS  PubMed  Google Scholar 

  16. Reháková Z, Capková J, Stĕpánková R, Sinkora J, Louzecká A, Ivanyi P, et al. Germ-free mice do not develop ankylosing enthesopathy, a spontaneous joint disease. Hum Immunol. 2000;61(6):555–8. https://doi.org/10.1016/s0198-8859(00)00122-1.

    Article  PubMed  Google Scholar 

  17. Caso F, Costa L, Chimenti MS, Navarini L, Punzi L. Pathogenesis of psoriatic arthritis. Crit Rev Immunol. 2019;39(5):361–77. https://doi.org/10.1615/CritRevImmunol.2020033243.

    Article  PubMed  Google Scholar 

  18. Winchester R, FitzGerald O. MHC class I associations beyond HLA-B27: the peptide binding hypothesis of psoriatic arthritis and its implications for disease pathogenesis. Curr Opin Rheumatol. 2020;32(4):330–6. https://doi.org/10.1097/BOR.0000000000000720.

    Article  CAS  PubMed  Google Scholar 

  19. Bárdos T, Zhang J, Mikecz K, David CS, Glant TT. Mice lacking endogenous major histocompatibility complex class II develop arthritis resembling psoriatic arthritis at an advanced age. Arthritis Rheum. 2002;46(9):2465–75. https://doi.org/10.1002/art.10637.

    Article  CAS  PubMed  Google Scholar 

  20. Bonfiglioli R, Conde RA, Sampaio-Barros PD, Louzada-Junior P, Donadi EA, Bertolo MB. Frequency of HLA-B27 alleles in Brazilian patients with psoriatic arthritis. Clin Rheumatol. 2008;27(6):709–12. https://doi.org/10.1007/s10067-007-0770-3.

    Article  PubMed  Google Scholar 

  21. Sandalova T, Michaëlsson J, Harris RA, Ljunggren HG, Kärre K, Schneider G, et al. Expression, refolding and crystallization of murine MHC class I H-2Db in complex with human beta2-microglobulin. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005;61(Pt 12):1090–3. https://doi.org/10.1107/S1744309105037942.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hammer RE, Maika SD, Richardson JA, Tang JP, Taurog JD. Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human beta 2m: an animal model of HLA-B27-associated human disorders. Cell. 1990;63(5):1099–112. https://doi.org/10.1016/0092-8674(90)90512-d.

    Article  CAS  PubMed  Google Scholar 

  23. Chenouard V, Remy S, Tesson L, Ménoret S, Ouisse LH, Cherifi Y, et al. Advances in genome editing and application to the generation of genetically modified rat models. Front Genet. 2021;20(12):615491. https://doi.org/10.3389/fgene.2021.615491.

    Article  CAS  Google Scholar 

  24. Khare SD, Luthra HS, David CS. Spontaneous inflammatory arthritis in HLA-B27 transgenic mice lacking beta 2-microglobulin: a model of human spondyloarthropathies. J Exp Med. 1995;182(4):1153–8. https://doi.org/10.1084/jem.182.4.1153.

    Article  CAS  PubMed  Google Scholar 

  25. Haider AS, Duculan J, Whynot JA, Krueger JG. Increased JunB mRNA and protein expression in psoriasis vulgaris lesions. J Investig Dermatol. 2006;126(4):912–4. https://doi.org/10.1038/sj.jid.5700183.

    Article  CAS  PubMed  Google Scholar 

  26. Zenz R, Eferl R, Kenner L, Florin L, Hummerich L, Mehic D, et al. Psoriasis-like skin disease and arthritis caused by inducible epidermal deletion of Jun proteins. Nature. 2005;437(7057):369–75. https://doi.org/10.1038/nature03963.

    Article  CAS  PubMed  Google Scholar 

  27. Taurog JD. Animal models of spondyloarthritis. Adv Exp Med Biol. 2009;649:245–54. https://doi.org/10.1007/978-1-4419-0298-6_18.

    Article  CAS  PubMed  Google Scholar 

  28. Fröhling M, Vogl T, Loser K. A1.30A key role of S100A9 in the pathogenesis of psoriatic arthritis in TTP/S100 deficient mice. Ann Rheum Dis. 2016;75(Suppl 1):A13.1. https://doi.org/10.1136/annrheumdis-2016-209124.30.

    Article  Google Scholar 

  29. Lu J, Squillace K, Pittelkow MR. Identification of the effect of amphiregulin on keratinocytes and T cells in psoriasis. Psoriasis Forum. 2010;16a(2):4–8. https://doi.org/10.1177/247553031016a00201.

    Article  Google Scholar 

  30. Cook PW, Brown JR, Cornell KA, Pittelkow MR. Suprabasal expression of human amphiregulin in the epidermis of transgenic mice induces a severe, early-onset, psoriasis-like skin pathology: expression of amphiregulin in the basal epidermis is also associated with synovitis. Exp Dermatol. 2004;13(6):347–56. https://doi.org/10.1111/j.0906-6705.2004.00183.x.

    Article  CAS  PubMed  Google Scholar 

  31. Migliorini E, Guevara-Garcia A, Albiges-Rizo C, Picart C. Learning from BMPs and their biophysical extracellular matrix microenvironment for biomaterial design. Bone. 2020;141:115540. https://doi.org/10.1016/j.bone.2020.115540.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Blessing M, Schirmacher P, Kaiser S. Overexpression of bone morphogenetic protein-6 (BMP-6) in the epidermis of transgenic mice: inhibition or stimulation of proliferation depending on the pattern of transgene expression and formation of psoriatic lesions. J Cell Biol. 1996;135(1):227–39. https://doi.org/10.1083/jcb.135.1.227.

    Article  CAS  PubMed  Google Scholar 

  33. Yahagi A, Saika T, Hirano H, Takai-Imamura M, Tsuji F, Aono H, et al. IL-6-PAD4 axis in the earliest phase of arthritis in knock-in gp130F759 mice, a model for rheumatoid arthritis. RMD Open. 2019;5(2):e000853. https://doi.org/10.1136/rmdopen-2018-000853.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Nakajima K, Kataoka S, Sato K, Takaishi M, Yamamoto M, Nakajima H, et al. Stat3 activation in epidermal keratinocytes induces Langerhans cell activation to form an essential circuit for psoriasis via IL-23 production. J Dermatol Sci. 2019;93(2):82–91. https://doi.org/10.1016/j.jdermsci.2018.11.007.

    Article  CAS  PubMed  Google Scholar 

  35. Yamamoto M, Nakajima K, Takaishi M, Kitaba S, Magata Y, Kataoka S, et al. Psoriatic inflammation facilitates the onset of arthritis in a mouse model. J Investig Dermatol. 2015;135(2):445–53. https://doi.org/10.1038/jid.2014.426.

    Article  CAS  PubMed  Google Scholar 

  36. Yang L, Fanok MH, Mediero-Munoz A, Fogli LK, Corciulo C, Abdollahi S, et al. Augmented Th17 differentiation leads to cutaneous and synovio-entheseal inflammation in a novel model of psoriatic arthritis. Arthritis Rheumatol. 2018;70(6):855–67. https://doi.org/10.1002/art.40447.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Stuart JM, Townes AS, Kang AH. Nature and specificity of the immune response to collagen in type II collagen-induced arthritis in mice. J Clin Investig. 1982;69(3):673–83. https://doi.org/10.1172/jci110495.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Courtenay JS, Dallman MJ, Dayan AD, Martin A, Mosedale B. Immunisation against heterologous type II collagen induces arthritis in mice. Nature. 1980;283(5748):666–8. https://doi.org/10.1038/283666a0.

    Article  CAS  PubMed  Google Scholar 

  39. Sakaguchi N, Takahashi T, Hata H, Nomura T, Tagami T, Yamazaki S, et al. Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice. Nature. 2003;426(6965):454–60. https://doi.org/10.1038/nature02119.

    Article  CAS  PubMed  Google Scholar 

  40. Jeong H, Bae EK, Kim H, Lim DH, Chung TY, Lee J, et al. Spondyloarthritis features in zymosan-induced SKG mice. Jt Bone Spine. 2018;85(5):583–91. https://doi.org/10.1016/j.jbspin.2017.11.008.

    Article  CAS  Google Scholar 

  41. Benham H, Rehaume LM, Hasnain SZ, Velasco J, Baillet AC, Ruutu M, et al. Interleukin-23 mediates the intestinal response to microbial β-1,3-glucan and the development of spondyloarthritis pathology in SKG mice. Arthritis Rheumatol. 2014;66(7):1755–67. https://doi.org/10.1002/art.38638.

    Article  CAS  PubMed  Google Scholar 

  42. Hagert C, Sareila O, Kelkka T, Jalkanen S, Holmdahl R. The macrophage mannose receptor regulate mannan-induced psoriasis, psoriatic arthritis, and rheumatoid arthritis-like disease models. Front Immunol. 2018;9:114. https://doi.org/10.3389/fimmu.2018.00114.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Khmaladze IA, Kelkka T, Guerard S, Wing K, Pizzolla A, Saxena A, et al. Mannan induces ROS-regulated, IL-17A-dependent psoriasis arthritis-like disease in mice. Proc Natl Acad Sci USA. 2014;111(35):E3669–78. https://doi.org/10.1073/pnas.1405798111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Zhong J, Scholz T, Yau ACY, Guerard S, Hüffmeier U, Burkhardt H, et al. Mannan-induced Nos2 in macrophages enhances IL-17-driven psoriatic arthritis by innate lymphocytes. Sci Adv. 2018;4(5):eaas9864. https://doi.org/10.1126/sciadv.aas9864.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Vecellio M, Hake VX, Davidson C, Carena MC, Wordsworth BP, Selmi C. The IL-17/IL-23 axis and its genetic contribution to psoriatic arthritis. Front Immunol. 2021;11:596086. https://doi.org/10.3389/fimmu.2020.596086.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Schinocca C, Rizzo C, Fasano S, Grasso G, La Barbera L, Ciccia F, et al. Role of the IL-23/IL-17 pathway in rheumatic diseases: an overview. Front Immunol. 2021;12:637829. https://doi.org/10.3389/fimmu.2021.637829.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Boutet MA, Nerviani A, Gallo Afflitto G, Pitzalis C. Role of the IL-23/IL-17 axis in psoriasis and psoriatic arthritis: the clinical importance of its divergence in skin and joints. Int J Mol Sci. 2018;19(2):530. https://doi.org/10.3390/ijms19020530.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Najm A, McInnes IB. IL-23 orchestrating immune cell activation in arthritis. Rheumatology (Oxford). 2021;60(Suppl 4):iv4–15. https://doi.org/10.1093/rheumatology/keab266.

    Article  CAS  PubMed  Google Scholar 

  49. Flores RR, Carbo L, Kim E, Van Meter M, De Padilla CML, Zhao J, et al. Adenoviral gene transfer of a single-chain IL-23 induces psoriatic arthritis-like symptoms in NOD mice. FASEB J. 2019;33(8):9505–15. https://doi.org/10.1096/fj.201900420R.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Mortier C, Gracey E, Coudenys J, Manuello T, Decruy T, Maelegheer M, Stappers F, Gilis E, Gaublomme D, Van Hoorebeke L, Van Welden S, Ambler C, Hegen M, Symanowicz P, Steyn S, Berstein G, Elewaut D, Venken K. RORγt inhibition ameliorates IL-23 driven experimental psoriatic arthritis by predominantly modulating γδ-T cells. Rheumatology (Oxford). 2023;20:kead022. https://doi.org/10.1093/rheumatology/kead022.

    Article  Google Scholar 

  51. Sheane BJ, Chandran V. Investigational drugs for treating psoriatic arthritis. Expert Opin Investig Drugs. 2014;23(7):1001–16. https://doi.org/10.1517/13543784.2014.910194.

    Article  CAS  PubMed  Google Scholar 

  52. Hagert C, Siitonen R, Li XG, Liljenbäck H, Roivainen A, Holmdahl R. Rapid spread of mannan to the immune system, skin and joints within 6 hours after local exposure. Clin Exp Immunol. 2019;196(3):383–91. https://doi.org/10.1111/cei.13268.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Yu K, Yu X, Cao S, Wang Y, Zhai Y, Yang F, et al. Layered dissolving microneedles as a need-based delivery system to simultaneously alleviate skin and joint lesions in psoriatic arthritis. Acta Pharm Sin B. 2021;11(2):505–19. https://doi.org/10.1016/j.apsb.2020.08.008.

    Article  CAS  PubMed  Google Scholar 

  54. Garcia-Hernandez M, Rangel-Moreno J, Paine A, Bhattacharya S, Fox J, Meyer E, et al. Psoriatic arthritis disease subtypes mediated by CD8 T cells are phenocopied in a novel humanized murine model of psoriasis and arthritis. Arthritis Rheumatol. 2022;74:4538–40.

    Google Scholar 

Download references

Acknowledgements

In writing this paper, I have benefited from the presence of my supervisors and my participators. They generously helped me collect materials I needed and made many invaluable suggestions. I hereby extend my grateful thanks to them for their kind help, without which the paper would not have been what it is.

Funding

This work was supported by the Shanxi Province Overseas Students Science and Technology Activities Merit-based Funding Project [Grant number 20210003].

Author information

Authors and Affiliations

Authors

Contributions

This article is mainly written by LB. YS wrote part of the manuscript and proofread the manuscript. ZN and CZ helped us collect literature information. GZ and LZ reviewed the manuscript and proposed final revisions. All authors contributed to the article and approved the submitted version.

Corresponding author

Correspondence to Gai-Lian Zhang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Consent for publication

Not applicable.

Additional information

Responsible Editor: John Di Battista.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 19 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bai, LK., Su, YZ., Ning, ZD. et al. Challenges and opportunities in animal models of psoriatic arthritis. Inflamm. Res. 72, 1291–1301 (2023). https://doi.org/10.1007/s00011-023-01752-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00011-023-01752-w

Keywords

Navigation