Loss of Kindlin-1 Causes Skin Atrophy and Lethal Neonatal Intestinal Epithelial Dysfunction: e1000289

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...

Full description

Saved in:
Bibliographic Details
Published in:PLoS genetics 2008-12, Vol.4 (12)
Main Authors: Ussar, Siegfried, Moser, Markus, Widmaier, Moritz, Rognoni, Emanuel, Harrer, Christian, Genzel-Boroviczeny, Orsolya, Fässler, Reinhard
Format: Article
Language:English
Subjects:
Cell adhesion & migration
Cellular biology
Colon
Mutation
Proteins
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 β 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.
ISSN:1553-7390
1553-7404
DOI:10.1371/journal.pgen.1000289