Loss of Kindlin-1 causes skin atrophy and lethal neonatal intestinal epithelial dysfunction.
Kindler Syndrome (KS), characterized by transient skin blistering followed by abnormal pigmentation, skin atrophy, and skin cancer, is caused by mutations in the FERMT1 gene. Although a few KS patients have been reported to also develop ulcerative colitis (UC), a causal link to the FERMT1 gene mutat...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2008-12-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC2585060?pdf=render |
| _version_ | 1818197055935348736 |
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| author | Siegfried Ussar Markus Moser Moritz Widmaier Emanuel Rognoni Christian Harrer Orsolya Genzel-Boroviczeny Reinhard Fässler |
| author_facet | Siegfried Ussar Markus Moser Moritz Widmaier Emanuel Rognoni Christian Harrer Orsolya Genzel-Boroviczeny Reinhard Fässler |
| author_sort | Siegfried Ussar |
| collection | DOAJ |
| description | Kindler Syndrome (KS), characterized by transient skin blistering followed by abnormal pigmentation, skin atrophy, and skin cancer, is caused by mutations in the FERMT1 gene. Although a few KS patients have been reported to also develop ulcerative colitis (UC), a causal link to the FERMT1 gene mutation is unknown. The FERMT1 gene product belongs to a family of focal adhesion proteins (Kindlin-1, -2, -3) that bind several beta integrin cytoplasmic domains. Here, we show that deleting Kindlin-1 in mice gives rise to skin atrophy and an intestinal epithelial dysfunction with similarities to human UC. This intestinal dysfunction results in perinatal lethality and is triggered by defective intestinal epithelial cell integrin activation, leading to detachment of this barrier followed by a destructive inflammatory response. |
| first_indexed | 2024-12-12T01:43:54Z |
| format | Article |
| id | doaj.art-c5a7a75627f64daf8f166e82cea7360e |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-12T01:43:54Z |
| publishDate | 2008-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-c5a7a75627f64daf8f166e82cea7360e2022-12-22T00:42:38ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042008-12-01412e100028910.1371/journal.pgen.1000289Loss of Kindlin-1 causes skin atrophy and lethal neonatal intestinal epithelial dysfunction.Siegfried UssarMarkus MoserMoritz WidmaierEmanuel RognoniChristian HarrerOrsolya Genzel-BoroviczenyReinhard FässlerKindler Syndrome (KS), characterized by transient skin blistering followed by abnormal pigmentation, skin atrophy, and skin cancer, is caused by mutations in the FERMT1 gene. Although a few KS patients have been reported to also develop ulcerative colitis (UC), a causal link to the FERMT1 gene mutation is unknown. The FERMT1 gene product belongs to a family of focal adhesion proteins (Kindlin-1, -2, -3) that bind several beta integrin cytoplasmic domains. Here, we show that deleting Kindlin-1 in mice gives rise to skin atrophy and an intestinal epithelial dysfunction with similarities to human UC. This intestinal dysfunction results in perinatal lethality and is triggered by defective intestinal epithelial cell integrin activation, leading to detachment of this barrier followed by a destructive inflammatory response.http://europepmc.org/articles/PMC2585060?pdf=render |
| spellingShingle | Siegfried Ussar Markus Moser Moritz Widmaier Emanuel Rognoni Christian Harrer Orsolya Genzel-Boroviczeny Reinhard Fässler Loss of Kindlin-1 causes skin atrophy and lethal neonatal intestinal epithelial dysfunction. PLoS Genetics |
| title | Loss of Kindlin-1 causes skin atrophy and lethal neonatal intestinal epithelial dysfunction. |
| title_full | Loss of Kindlin-1 causes skin atrophy and lethal neonatal intestinal epithelial dysfunction. |
| title_fullStr | Loss of Kindlin-1 causes skin atrophy and lethal neonatal intestinal epithelial dysfunction. |
| title_full_unstemmed | Loss of Kindlin-1 causes skin atrophy and lethal neonatal intestinal epithelial dysfunction. |
| title_short | Loss of Kindlin-1 causes skin atrophy and lethal neonatal intestinal epithelial dysfunction. |
| title_sort | loss of kindlin 1 causes skin atrophy and lethal neonatal intestinal epithelial dysfunction |
| url | http://europepmc.org/articles/PMC2585060?pdf=render |
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