Targeted Transgenic Expression of the Mutation Causing Hutchinson-Gilford Progeria Syndrome Leads to Proliferative and Degenerative Epidermal Disease

The study explored the effects of the mutation causing Hutchinson-Gilford progeria syndrome (HGPS) in transgenic mice, focusing on skin pathology. Researchers found that mice expressing the mutant lamin A (progerin) exhibited significant skin abnormalities, including epidermal hyperplasia, hyperkeratosis, and changes in sebaceous glands, with severe cases showing fibrosis and inflammatory cell invasion. These mice also experienced hair thinning, growth retardation, and premature death, with a median survival of 14 weeks. The severity of these defects was linked to the level of transgene expression. The study provided insights into the pathological mechanisms of HGPS, highlighting the role of lamin A and progerin in skin disease and systemic effects, and suggested potential areas for therapeutic intervention.