| First Author | Miyamoto K | Year | 2003 |
| Journal | Eur J Immunol | Volume | 33 |
| Issue | 3 | Pages | 656-65 |
| PubMed ID | 12616486 | Mgi Jnum | J:82432 |
| Mgi Id | MGI:2652985 | Doi | 10.1002/eji.200323677 |
| Citation | Miyamoto K, et al. (2003) Heterozygous null mutation of myelin P0 protein enhances susceptibility to autoimmune neuritis targeting P0 peptide. Eur J Immunol 33(3):656-65 |
| abstractText | 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. |
