Harlequin Ichthyosis (ICHQ): A Juvenile Lethal Mouse Mutation with Ichthyosiform Dermatitis

The harlequin ichthyosis (ichq) mouse mutation, discovered in 1989 in BALB/cJ mice, resulted in thick skin with compact, orthokeratotic scales and was lethal by 9-12 days of age. The clinical phenotype appeared at 5 days, coinciding with hair fiber emergence. Affected mice exhibited marked proliferation of anagen hair follicle root sheaths, small sebaceous glands, and thick cornified sheaths around hair fibers. Ultrastructural analysis revealed large mitochondria with lamellar structures and smaller keratohyalin granules. Keratin 6 was overexpressed, while loricrin expression decreased rapidly postmortem. Skin grafts maintained the phenotype for 10 weeks. The mutation mapped to chromosome 19 and was autosomal recessive, resembling human type 2 harlequin ichthyosis.