Linked Life Data

9490728

Source:http://linkedlifedata.com/resource/pubmed/id/9490728

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pubmed-article:9490728pubmed:abstractTextMice carrying the Tight skin (Tsk) mutation harbor a genomic duplication within the fibrillin-1 (Fbn 1) gene that results in a larger than normal in-frame Fbn 1 transcript. In this study, the consequences of the Tsk mutation for fibrillin-containing microfibrils have been examined. Dermal fibroblasts from Tsk/+ mice synthesized and secreted both normal fibrillin (approximately 330 kD) and the mutant oversized Tsk fibrillin-1 (approximately 450 kD) in comparable amounts, and Tsk fibrillin-1 was stably incorporated into cell layers. Immunohistochemical and ultrastructural analyses of normal and Tsk/+ mouse skin highlighted differences in the gross organization and distribution of microfibrillar arrays. Rotary shadowing of high Mr preparations from Tsk/+ skin demonstrated the presence of abundant beaded microfibrils. Some of these had normal morphology and periodicity, but others were distinguished by diffuse interbeads, longer periodicity, and tendency to aggregate. The presence of a structurally abnormal population of microfibrils in Tsk/+ skin was unequivocally demonstrated after calcium chelation and in denaturating conditions. Scanning transmission electron microscopy highlighted the presence of more mass in Tsk/+ skin microfibrils than in normal mice skin microfibrils. These data indicate that Tsk fibrillin-1 polymerizes and becomes incorporated into a discrete population of beaded microfibrils with altered molecular organization.lld:pubmed
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pubmed-article:9490728pubmed:authorpubmed-author:JimenezS ASAlld:pubmed
pubmed-article:9490728pubmed:authorpubmed-author:PetersRRlld:pubmed
pubmed-article:9490728pubmed:authorpubmed-author:KieltyC MCMlld:pubmed
pubmed-article:9490728pubmed:authorpubmed-author:SiracusaL DLDlld:pubmed
pubmed-article:9490728pubmed:authorpubmed-author:RaghunathMMlld:pubmed
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pubmed-article:9490728pubmed:dateRevised2009-11-18lld:pubmed
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pubmed-article:9490728pubmed:articleTitleThe Tight skin mouse: demonstration of mutant fibrillin-1 production and assembly into abnormal microfibrils.lld:pubmed
pubmed-article:9490728pubmed:affiliationSchool of Biological Sciences, University of Manchester, Manchester, M13 9PT, United Kingdom. cay.kielty@man.ac.uklld:pubmed
pubmed-article:9490728pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:9490728pubmed:publicationTypeResearch Support, U.S. Gov't, P.H.S.lld:pubmed
pubmed-article:9490728pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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