title: Development of an improved animal model of experimental autoimmune myositis.
abstract: Multiple animal models of experimental autoimmune myositis (EAM) have been developed. However, these models vary greatly in the severity of disease and reproducibility. The goal of this study was to test whether vaccination twice with increased dose of rat myosin and pertussis toxin (PT) could induce EAM with severer disease in mice. BALB/c mice were injected with 1 mg rat myosin in 50% complete Freund's adjuvant (CFA) weekly for four times and one time of PT (EAM) or twice with 1.5 mg myosin in CFA and PT (M-EAM). In comparison with that in the CFA and PT injected controls, vaccination with rat myosin and injection PT significantly reduced the muscle strength and EMG duration, elevated serum creatine kinase levels, promoted inflammatory infiltration in the muscle tissues, leading to pathological changes in the muscle tissues, demonstrating to induce EAM. Interestingly, we found that vaccination twice with the high dose of myosin and PT prevented EAM-related gain in body weights and caused significantly less muscle strength in mice. More importantly, all of the mice receiving high dose of myosin and PT survived while 3 out of 16 mice with four times of low dose of myosin died. Finally, vaccination with high dose of myosin promoted CD4(+) and CD8(+) T cell infiltration in the muscle tissues and up-regulated MHC-I expression in the muscle tissues of mice. Hence, the new model of EAM is a time-saving, efficient and easily replicable tool for studying autoimmune myositis.
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University Xi'an, Shaanxi, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Kang
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University Xi'an, Shaanxi, China.
authors.forename: Hong-Ya
authors.initials: HY
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University Xi'an, Shaanxi, China.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Feng
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University Xi'an, Shaanxi, China.
authors.forename: Dong-Yun
authors.initials: DY
authors.lastname: Feng
authors.affiliation: Department of Neurology, Xijing Hospital, The Fourth Military Medical University Xi'an, Shaanxi, China.
authors.forename: Hong-Ge
authors.initials: HG
authors.lastname: Jia
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002634:Chemotaxis, Leukocyte; D052283:Creatine Kinase, MM Form / Q000097:blood; D018450:Disease Progression; D005260:Female; D006168:Guinea Pigs; D008807:Mice, Inbred BALB C; D053580:Muscle Strength; D018482:Muscle, Skeletal / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009218:Myosins; D020721:Nervous System Autoimmune Disease, Experimental / Q000097:blood / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D037342:Pertussis Toxin; D010641:Phenotype; D012720:Severity of Illness Index; D013997:Time Factors; D015430:Weight Gain
chemical_list: D015415:Biomarkers; D037342:Pertussis Toxin; D052283:Creatine Kinase, MM Form; D009218:Myosins
keywords: Experimental autoimmune myositis (EAM); animal models; idiopathic inflammatory myopathies (IIM); immunosuppressive
references.citation: J Neuroimmunol. 2007 Oct;190(1-2):90-100
references.pmid: 17900708
references.citation: Behav Brain Res. 2001 Sep 28;124(1):33-46
references.pmid: 11423164
references.citation: Am J Ther. 2015 Jul-Aug;22(4):244-7
references.pmid: 25490616
references.citation: Skelet Muscle. 2014 Aug 04;4:16
references.pmid: 25161767
references.citation: N Engl J Med. 1991 Nov 21;325(21):1487-98
references.pmid: 1658649
references.citation: Blood. 2008 Sep 1;112(5):1813-21
references.pmid: 18550850
references.citation: Lancet. 2003 Sep 20;362(9388):971-82
references.pmid: 14511932
references.citation: Curr Opin Rheumatol. 2009 Nov;21(6):610-6
references.pmid: 19726994
references.citation: Int Immunol. 2015 Jul;27(7):327-32
references.pmid: 25577193
references.citation: Cochrane Database Syst Rev. 2012;8:CD003643
references.pmid: 22895935
references.citation: Acta Neuropathol. 1993;85(2):138-44
references.pmid: 8442405
references.citation: Clin Dev Immunol. 2012;2012:369432
references.pmid: 22110532
references.citation: Proc Natl Acad Sci U S A. 2000 Aug 1;97(16):9209-14
references.pmid: 10922072
references.citation: J Neurol Sci. 1997 Oct 22;151(2):141-8
references.pmid: 9349668
references.citation: J Neurol Sci. 1996 Dec;144(1-2):171-5
references.pmid: 8994120
references.citation: Am J Pathol. 2009 Mar;174(3):989-98
references.pmid: 19218348
references.citation: Curr Opin Neurol. 2001 Oct;14(5):591-6
references.pmid: 11562570
references.citation: J Neurol Neurosurg Psychiatry. 2000 Apr;68(4):472-8
references.pmid: 10727483
references.citation: Arthritis Rheumatol. 2015 Apr;67(4):1107-16
references.pmid: 25580817
references.citation: Rheum Dis Clin North Am. 2002 Nov;28(4):723-41
references.pmid: 12510664
references.citation: Rheum Dis Clin North Am. 2002 Nov;28(4):779-98, vi
references.pmid: 12506772
references.citation: J Immunol. 2006 Aug 1;177(3):1552-60
references.pmid: 16849462
references.citation: J Neuroimmunol. 1999 Aug 3;98(2):130-5
references.pmid: 10430046
references.citation: Nat Rev Rheumatol. 2010 Mar;6(3):129-37
references.pmid: 20125096