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 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.