HARLEQUIN ICHTHYOSIS (ICHQ) - A JUVENILE LETHAL MOUSE MUTATION WITH ICHTHYOSIFORM DERMATITIS

The harlequin ichthyosis (ichq) mouse mutation arose spontaneously in 1989 in a colony of BALB/cJ mice at The Jackson Laboratory, Affected m ice developed thick skin due to formation of compact, orthokeratotic s cales that fractured over articular surfaces, secondary to bending Har lequin ichthyosis mice on the inbred BALB/cJ background died between 9 and 12 days of age. Onset of the clinical phenotype corresponded with emergence of hair fibers from follicles at 5 days of age, There was m arked proliferation of the root sheaths of anagen hair follicles, limi ted to the region within the dermis. Sebaceous glands were present but small compared with those of littermate controls, Emerging hair fiber s were surrounded by a thick, compact sheath of cornified cells, Mutan t skin contained large mitochondria with lamellar-shaped, electron-den se structures at the ultrastructural level, Keratohyalin granules were smaller and less pleomorphic than those in control mice. Lamellar bod ies were not evident in either mutant or littermate control mice. Usin g a panel of antibodies to evaluate changes in keratinocyte differenti ation, mouse-specific keratin 6 was overexpressed in the suprabasilar, hyperplastic epidermis, Loricrin expression, within the cytoplasm of cells in the stratum granulosum, decreased rapidly postmortem, unlike that in normal mice where it was stable for over 24 hours postmortem, Filaggrin expression, within granules of cells in the stratum granulos um, was prominent, corresponding to hypergranulosis evident by light m icroscopy in mutant mouse skin, Skin grafts from harlequin ichthyosis mice grafted onto immunodeficient nude mice maintained the phenotype f or the 10-week observation period, The mutant gene locus napped to the proximal end of mouse chromosome 19 and is inherited as a fully penet rant autosomal recessive gene, The harlequin ichthyosis mouse mutation is very similar to human type 2 harlequin ichthyosis for which it may be a good model.