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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...

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Autores principales: Guo, Yanan, Dreier, John R., Cao, Juxiang, Du, Heng, Granter, Scott R., Kwiatkowski, David J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
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.
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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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