RNA Expression Analysis of Passive Transfer Myasthenia Supports Extraocular Muscle as a Unique Immunological Environment

Abstract

Our studies demonstrated that consistent with human myasthenia gravis, EOM demonstrates a distinct RNA expression signature from EDL and diaphragm, which is based on differences in the degree of muscle injury and inflammatory response.

Differential RNA Expression Profile of Skeletal Muscle Induced by Experimental Autoimmune Myasthenia Gravis in Rats

“…The GAPDH probes 3–5 ratio ranged from 1.06 to 2.66 with average 1.27 ± 0.35, indicating RNA quality was appropriate and the hybridization was successful among the samples. The results are consistent with our previous expression profiling studies (Zhou et al, 2014). …”

“…In our previous study of passive transfer MG and a study of mdx mice (Porter et al, 2003a; Zhou et al, 2014), we determined a disease load index (DLI), which sums the absolute fold change values of increased and decreased transcript to provide a single transcriptional index of EAMG pathology. In the present investigation, EDL had the greatest DLI (Figure 3), although EOM had the greatest total of increased transcript levels with 351 total fold increase to 101 total fold decrease.…”

“…Three upregulated transcripts ( Ankrd1, Mt1a, Cebpd1 ) and one down regulated transcript ( Neu2 ) that by RNA profiling had been identified as altered across all three muscles. We assessed transcripts that were previously identified as altered by EAMG ( Chrna1, Pde4b, Cts1, Trm63 ) (Mizrachi et al, 2010; Zhou et al, 2014) or involved in inflammation ( NF κ B, Ctse ). We evaluated transcripts that were increased in the RNA profiling of EOM alone ( Plunc, Pax6, Rgs2 ) (Porter et al, 2003b) or known to be increased in EOM ( Csrp3 ) (Diehl et al, 2006).…”

“…The extremely rapid firing rate of ocular motor neurons and the immature appearance of their neuromuscular junctions may place the EOM at particular risk for a neuromuscular transmission disorder. The RNA expression profiles of EOM, extensor digitorum longus (EDL), and diaphragm (DIA) muscle from rats with passively-transferred MG (PTMG) (Kusner et al, 2015) produced by administration of acetylcholine receptor antibody supports a greater degree of injury to EOM (Zhou et al, 2014), which supports that EOM has unique immunological characteristics that places them at specific risk for MG (Kaminski et al, 2004; Soltys et al, 2008; Pedrosa Domellof, 2013). …”

Guidelines for pre-clinical assessment of the acetylcholine receptor-specific passive transfer myasthenia gravis model—Recommendations for methods and experimental designs

“…Monoclonal Ab198 (Tzartos et al, 1983) also produced weakness in the rat (Hwang et al, 2003). mAb3 (Lennon and Lambert, 1981) showed extensive complement mediated damage to the NMJ of rats (Zhou et al, 2007; Ruff and Lennon, 2008; Soltys et al, 2009; Kusner et al, 2014; Zhou et al, 2014). …”