Ectoderm-Targeted Overexpression of the Glucocorticoid Receptor Induces Hypohidrotic Ectodermal Dysplasia

The study investigated the effects of ectoderm-targeted overexpression of the glucocorticoid receptor (GR) in transgenic mice, which led to hypohidrotic ectodermal dysplasia-like symptoms. These mice exhibited defects in hair follicle, tooth, and palate development, lacked Meibomian glands, and had underdeveloped sweat and preputial glands. The study found that these defects were due to decreased NF-kappaB activity, caused by functional antagonism between GR and NF-kappaB. The use of dexamethasone in wild-type mice induced similar defects, suggesting the role of ligand-activated GR. The research highlighted reduced expression of IKK subunits and p65 protein in K5-GR mice, leading to decreased kappaB-binding activity and reduced DeltaNp63 protein levels in tooth epithelia. These findings suggested that understanding the molecular mechanisms in this mouse model could provide insights into other ectodermal dysplasia syndromes.