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The pathophysiological phenotype of CMT1A is aberrant axonal myelination which induces a reduction in nerve conduction velocity (NCV). Several CMT1A model rodents have been established by overexpressing <jats:italic>pmp22<\/jats:italic>. Thus, it is thought that <jats:italic>pmp22<\/jats:italic> expression must be tightly regulated for correct myelin formation in mammals. Interestingly, the myelin sheath is also present in other jawed vertebrates. The purpose of this study is to analyze the evolutionary conservation of the association between <jats:italic>pmp22<\/jats:italic> transcription level and vertebrate myelin formation, and to find the conserved non-coding sequences for <jats:italic>pmp22<\/jats:italic> regulation by comparative genomics analyses between jawed fishes and mammals.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>A transgenic <jats:italic>pmp22<\/jats:italic> over-expression medaka fish line was established. The transgenic fish had approximately one fifth the peripheral NCV values of controls, and aberrant myelination of transgenic fish in the peripheral nerve system (PNS) was observed. We successfully confirmed that medaka fish <jats:italic>pmp22<\/jats:italic> has the same exon-intron structure as mammals, and identified some known conserved regulatory motifs. Furthermore, we found novel conserved sequences in the first intron and 3'UTR.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Medaka fish undergo abnormalities in the PNS when <jats:italic>pmp22<\/jats:italic> transcription increases. This result indicates that an adequate <jats:italic>pmp22<\/jats:italic> transcription level is necessary for correct myelination of jawed vertebrates. Comparison of <jats:italic>pmp22<\/jats:italic> orthologs between distantly related species identifies evolutionary conserved sequences that contribute to precise regulation of <jats:italic>pmp22<\/jats:italic> expression.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2202-10-60","type":"journal-article","created":{"date-parts":[[2009,6,17]],"date-time":"2009-06-17T18:14:51Z","timestamp":1245262491000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Functional and comparative genomics analyses of pmp22 in medaka fish"],"prefix":"10.1186","volume":"10","author":[{"given":"Junji","family":"Itou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikita","family":"Suyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Imamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonori","family":"Deguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Fujimori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Yuba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaka","family":"Kawarabayasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Kawasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2009,6,17]]},"reference":[{"issue":"1","key":"1064_CR1","doi-asserted-by":"publisher","first-page":"R29","DOI":"10.1016\/j.cub.2006.11.042","volume":"17","author":"DK Hartline","year":"2007","unstructured":"Hartline DK, Colman DR: Rapid conduction and the evolution of giant axons and myelinated fibers. 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