A Spontaneous Fatp4/Slc27a4 Splice Site Mutation in a New Murine Model for Congenital Ichthyosis

The study identified a novel recessive mutation in mice that led to newborn lethality with severe congenital lamellar ichthyosis, resembling human autosomal-recessive congenital ichthyosis. The genetic defect was linked to the Fatp4/Slc27a4 gene, with a specific A to T mutation causing a splice site error and exon 9 deletion, resulting in a frame shift mutation. This mutation affected keratinocyte differentiation, caused hyperproliferation of the stratum basale, a hyperkeratotic stratum corneum, and reduced secondary hair follicles. The findings suggested that very long chain fatty acids are crucial for normal skin differentiation and may influence signaling from the stratum corneum to basal cells.