{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T05:32:27Z","timestamp":1770096747905,"version":"3.49.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2004,2,1]],"date-time":"2004-02-01T00:00:00Z","timestamp":1075593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2004,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Genetic deficiency or instability of myelin protein zero (P0) results in hereditary motor sensory neuropathy. In view of recent advances in gene therapy, substitution of the molecular defect may become realistic in the near future. Here we investigate the impact of genetic deficiency of P0 on selection of the autoreactive T cell repertoire in the corresponding mouse model. We show that P0 mRNA transcripts are expressed in thymic stroma, similar to other myelin proteins and that expression of intact P0 protein can be detected by Western blot. Using a library of overlapping 20mer peptides spanning the entire length of P0 and applying the ELISPOT technique, we detected a strong immune response toward P0 extracellular domain peptide aa 41\u201360 in P0\u2212\/\u2212 knockout mice, but not in heterozygous P0+\/\u2212 or wild-type (wt) mice. In addition, one cryptic epitope and two subdominant epitopes of P0 were identified. Using P0\u2212\/\u2212 into wt bone marrow (BM) chimeras we found that P0 expression in the host suffices for full tolerance induction, which is in line with its presence in thymic stroma. However, repopulation of P0\u2212\/\u2212 mice with wt BM led to partial induction of tolerance, suggesting that BM derived cells can also express this protein. Our findings may have implications for secondary autoimmunity developing after gene therapy in hereditary neuropathies and other diseases with genetically determined protein deficiency, because the repaired protein will then represent a foreign, nontolerized Ag.<\/jats:p>","DOI":"10.4049\/jimmunol.172.3.1364","type":"journal-article","created":{"date-parts":[[2014,4,20]],"date-time":"2014-04-20T21:08:36Z","timestamp":1398028116000},"page":"1364-1370","source":"Crossref","is-referenced-by-count":12,"title":["Tolerance Induction by Intrathymic Expression of P0"],"prefix":"10.1093","volume":"172","author":[{"given":"Lucian","family":"Visan","sequence":"first","affiliation":[{"name":"Department of Neurology, Clinical Research Group for Multiple Sclerosis and Neuroimmunology, University of Wu\u0308rzburg , Wu\u0308rzburg ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ioana A","family":"Visan","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Wu\u0308rzburg , Wu\u0308rzburg ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Weishaupt","sequence":"additional","affiliation":[{"name":"Department of Neurology, Clinical Research Group for Multiple Sclerosis and Neuroimmunology, University of Wu\u0308rzburg , Wu\u0308rzburg ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harald H","family":"Hofstetter","sequence":"additional","affiliation":[{"name":"Department of Neurology, Clinical Research Group for Multiple Sclerosis and Neuroimmunology, University of Wu\u0308rzburg , Wu\u0308rzburg ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Klaus V","family":"Toyka","sequence":"additional","affiliation":[{"name":"Department of Neurology, Clinical Research Group for Multiple Sclerosis and Neuroimmunology, University of Wu\u0308rzburg , Wu\u0308rzburg ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Hu\u0308nig","sequence":"additional","affiliation":[{"name":"Institute for Virology and Immunobiology, University of Wu\u0308rzburg , Wu\u0308rzburg ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Gold","sequence":"additional","affiliation":[{"name":"Department of Neurology, Clinical Research Group for Multiple Sclerosis and Neuroimmunology, University of Wu\u0308rzburg , Wu\u0308rzburg ,","place":["Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2004,2,1]]},"reference":[{"key":"2026020211184777100_R1","first-page":"244","volume-title":"J. 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