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Analysis of a Mouse Skin Model of Tuberous Sclerosis Complex
Tuberous Sclerosis Complex (TSC) is an autosomal dominant tumor suppressor gene syndrome in which patients develop several types of tumors, including facial angiofibroma, subungual fibroma, Shagreen patch, angiomyolipomas, and lymphangioleiomyomatosis. It is due to inactivating mutations in TSC1 or...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5132223/ https://www.ncbi.nlm.nih.gov/pubmed/27907099 http://dx.doi.org/10.1371/journal.pone.0167384 |
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author | Guo, Yanan Dreier, John R. Cao, Juxiang Du, Heng Granter, Scott R. Kwiatkowski, David J. |
author_facet | Guo, Yanan Dreier, John R. Cao, Juxiang Du, Heng Granter, Scott R. Kwiatkowski, David J. |
author_sort | Guo, Yanan |
collection | PubMed |
description | Tuberous Sclerosis Complex (TSC) is an autosomal dominant tumor suppressor gene syndrome in which patients develop several types of tumors, including facial angiofibroma, subungual fibroma, Shagreen patch, angiomyolipomas, and lymphangioleiomyomatosis. It is due to inactivating mutations in TSC1 or TSC2. We sought to generate a mouse model of one or more of these tumor types by targeting deletion of the Tsc1 gene to fibroblasts using the Fsp-Cre allele. Mutant, Tsc1(cc)Fsp-Cre+ mice survived a median of nearly a year, and developed tumors in multiple sites but did not develop angiomyolipoma or lymphangioleiomyomatosis. They did develop a prominent skin phenotype with marked thickening of the dermis with accumulation of mast cells, that was minimally responsive to systemic rapamycin therapy, and was quite different from the pathology seen in human TSC skin lesions. Recombination and loss of Tsc1 was demonstrated in skin fibroblasts in vivo and in cultured skin fibroblasts. Loss of Tsc1 in fibroblasts in mice does not lead to a model of angiomyolipoma or lymphangioleiomyomatosis. |
format | Online Article Text |
id | pubmed-5132223 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-51322232016-12-21 Analysis of a Mouse Skin Model of Tuberous Sclerosis Complex Guo, Yanan Dreier, John R. Cao, Juxiang Du, Heng Granter, Scott R. Kwiatkowski, David J. PLoS One Research Article Tuberous Sclerosis Complex (TSC) is an autosomal dominant tumor suppressor gene syndrome in which patients develop several types of tumors, including facial angiofibroma, subungual fibroma, Shagreen patch, angiomyolipomas, and lymphangioleiomyomatosis. It is due to inactivating mutations in TSC1 or TSC2. We sought to generate a mouse model of one or more of these tumor types by targeting deletion of the Tsc1 gene to fibroblasts using the Fsp-Cre allele. Mutant, Tsc1(cc)Fsp-Cre+ mice survived a median of nearly a year, and developed tumors in multiple sites but did not develop angiomyolipoma or lymphangioleiomyomatosis. They did develop a prominent skin phenotype with marked thickening of the dermis with accumulation of mast cells, that was minimally responsive to systemic rapamycin therapy, and was quite different from the pathology seen in human TSC skin lesions. Recombination and loss of Tsc1 was demonstrated in skin fibroblasts in vivo and in cultured skin fibroblasts. Loss of Tsc1 in fibroblasts in mice does not lead to a model of angiomyolipoma or lymphangioleiomyomatosis. Public Library of Science 2016-12-01 /pmc/articles/PMC5132223/ /pubmed/27907099 http://dx.doi.org/10.1371/journal.pone.0167384 Text en © 2016 Guo et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Guo, Yanan Dreier, John R. Cao, Juxiang Du, Heng Granter, Scott R. Kwiatkowski, David J. Analysis of a Mouse Skin Model of Tuberous Sclerosis Complex |
title | Analysis of a Mouse Skin Model of Tuberous Sclerosis Complex |
title_full | Analysis of a Mouse Skin Model of Tuberous Sclerosis Complex |
title_fullStr | Analysis of a Mouse Skin Model of Tuberous Sclerosis Complex |
title_full_unstemmed | Analysis of a Mouse Skin Model of Tuberous Sclerosis Complex |
title_short | Analysis of a Mouse Skin Model of Tuberous Sclerosis Complex |
title_sort | analysis of a mouse skin model of tuberous sclerosis complex |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5132223/ https://www.ncbi.nlm.nih.gov/pubmed/27907099 http://dx.doi.org/10.1371/journal.pone.0167384 |
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