title: Animal models of antineutrophil cytoplasm antibody-associated vasculitis.
abstract: OBJECTIVE
  To provide an update on the experimental models that have been developed recapitulating clinical antineutrophil cytoplasm antibody (ANCA) associated vasculitis. The application of the models in the study of pathogenesis, and the therapeutic implications of this, are covered in the article by van Timmeren and Heeringa in this issue.
  
  
  RESULTS
  Rodent models of both myeloperoxidase (MPO) ANCA and proteinase 3 (PR3) ANCA associated vasculitis have been developed, which have provided important insights into the pathogenesis of ANCA-associated pulmonary and renal disease. The vast majority of in-vivo work in this field has concerned MPO-ANCA associated disease, although the last year has seen some advances in the modelling of anti-PR3 disease. As with all experimental animal models, they are flawed in one way or another by virtue of the means by which they are induced, but they have already provided novel directions for future intervention in these complex diseases. To date, there are no good models that replicate the granulomatous lesions found in granulomatosis with polyangiitis (GPA, formerly Wegener's) or the development of vasculitis lesions in organs other than the lungs or kidneys.
  
  
  CONCLUSIONS
  ANCA-associated vasculitis can be induced in various forms in susceptible rodents. Further refinements are required for the full spectrum of disease phenotype to be replicated in animals, but critical new targets have been proposed based on the use of molecular blocking agents and transgenic animals to elucidate disease pathways.
authors.affiliation: UCL Centre for Nephrology Royal Free Hospital, London, UK. a.salama@ucl.ac.uk
authors.forename: Alan D
authors.initials: AD
authors.lastname: Salama
authors.forename: Mark A
authors.initials: MA
authors.lastname: Little
mesh_terms: D000818:Animals; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D051381:Rats
references.citation: Arthritis Rheum. 2011 Apr;63(4):1124-35
references.pmid: 21190299
references.citation: Kidney Int. 2003 Jul;64(1):140-8
references.pmid: 12787404
references.citation: Nat Med. 2008 Oct;14(10):1088-96
references.pmid: 18836458
references.citation: Am J Pathol. 2005 Jul;167(1):39-45
references.pmid: 15972950
references.citation: Nephrol Dial Transplant. 2010 Jul;25(7):2209-17
references.pmid: 20100727
references.citation: J Am Soc Nephrol. 2006 Jul;17(7):1940-9
references.pmid: 16769746
references.citation: Arthritis Rheum. 2010 May;62(5):1539-48
references.pmid: 20155828
references.citation: Blood. 2004 Sep 1;104(5):1411-8
references.pmid: 15150076
references.citation: Am J Pathol. 2005 Jul;167(1):47-58
references.pmid: 15972951
references.citation: Am J Pathol. 2009 Apr;174(4):1212-20
references.pmid: 19264905
references.citation: Am J Pathol. 2007 Jan;170(1):52-64
references.pmid: 17200182
references.citation: J Am Soc Nephrol. 2010 Jun;21(6):925-31
references.pmid: 20299361
references.citation: Contrib Nephrol. 2011;169:211-220
references.pmid: 21252521
references.citation: Ann Rheum Dis. 2007 Dec;66(12):1679-82
references.pmid: 17644551
references.citation: Nature. 2006 Feb 16;439(7078):851-5
references.pmid: 16482158
references.citation: J Am Soc Nephrol. 2006 Dec;17(12):3355-64
references.pmid: 17108314
references.citation: J Clin Invest. 2002 Oct;110(7):955-63
references.pmid: 12370273
references.citation: Clin Exp Immunol. 2010 Mar;159(3):327-37
references.pmid: 20015271
references.citation: Blood. 2005 Sep 15;106(6):2050-8
references.pmid: 15933057