1. P0 protein peptide 180-199 together with pertussis toxin induces experimental autoimmune neuritis in resistant C57BL/6 mice
L P Zou, H G Ljunggren, M Levi, I Nennesmo, B Wahren, E Mix, B Winblad, M Schalling, J Zhu J Neurosci Res. 2000 Dec 1;62(5):717-21. doi: 10.1002/1097-4547(20001201)62:53.0.CO;2-P.
The C57BL/6 mice strain is known to be reputedly resistant to induction of experimental autoimmune neuritis (EAN), an animal model of Guillain-Barré syndrome in human by bovine peripheral myelin (BPM), and P2 protein or the P2 protein peptide 57-81. The P0 peptide 180-199 is a stronger neuritogenic antigen than the P2 peptide 57-81. We found that this synthetic peptide induced both clinical and pathological characteristics of an acute monophasic EAN in C57BL/6 mice. Only male mice were more sensitive to EAN induction with the P0 peptide 180-199. Intravenously administrated pertussis toxin (PT) had an adjuvant effect that increased the incidence of P0 peptide 180-199-induced EAN as well as the inflammation and demyelination in the peripheral nerves. Spontaneous and P0 peptide 180-199 stimulated proliferation of peripheral T-cells were enhanced by PT-treatment as well. The enhancing effect was lower before onset of the disease (Day 6 post immunization) (p.i.) as compared to the early phase of the disease (Day 22 p.i.). Thus, P0 peptides together with PT are able to break tolerance to myelin in C57BL/6 mice.
2. Myelin Protein Zero180-199 Peptide Induced Experimental Autoimmune Neuritis in C57BL/6 Mice
David G Gonsalvez, SangWon Yoo, Georgina A Craig, Rhiannon J Wood, Jessica L Fletcher, Simon S Murray, Junhua Xiao Methods Mol Biol. 2018;1791:243-250. doi: 10.1007/978-1-4939-7862-5_19.
Mouse models of peripheral demyelinating neuropathy play an important role in enabling the study of disease pathogenesis. Further, induction in transgenic mice allows for the precise interrogation of disease mechanisms, as well as the analysis of the efficacy and mechanisms of potential new therapies. Here we describe a method to successfully induce experimental autoimmune neuritis (EAN) using myelin protein zero (P0)180-199 peptide in combination with Freund's complete adjuvant and pertussis toxin in the C57BL/6 mouse strain. We also outline a sensitive paradigm of accurately assessing the extent of functional deficits occurring in murine EAN.
3. Heterozygous null mutation of myelin P0 protein enhances susceptibility to autoimmune neuritis targeting P0 peptide
Katsuichi Miyamoto, Sachiko Miyake, Melitta Schachner, Takashi Yamamura Eur J Immunol. 2003 Mar;33(3):656-65. doi: 10.1002/eji.200323677.
Mice with a heterozygous null mutation in myelin protein zero (P0(+/-)) develop late-onset clinical paralysis associated with inflammatory pathology in the peripheral nerves. Although the development of this illness is known to require T cells and macrophages, little is understood regarding the immunological defect in the mice. Here we report that young P0(+/-) mice, free from clinical manifestations, have a defect in central tolerance to P0, and are more prone to induction of experimental autoimmune neuritis (EAN) by sensitization against P0(180-199 )peptide. Notably, we found that the P0 gene is transcribed in the thymus of wild-type and the P0(+/-) mice in an amount proportional to the gene dosage. We then replaced the thymus of wild-type mice with that of the P0-deficient mice and vice versa. Immunization of these mice with P0(180-199 )revealed that a lower thymic P0 transcript would be associated with the higher recall T cell response to P0(180-199), thus accounting for the higher susceptibility of the P0(+/-) mice to P0-induced EAN. These results imply that a heterozygous mutation in an autoantigen could cause defective central tolerance to the autoantigen. As such, autoimmune T cells may play some role in "genetic" diseases caused by a heterozygous gene defect.
