Cutaneous ultrastructural features of the flaky skin (fsn) mouse mutation. Morita K,Hogan M E,Nanney L B,King L E,Manabe M,Sun T T,Sundberg J P The Journal of dermatology An autosomal recessive genetic disease with clinical and histopathological skin features resembling human psoriasis vulgaris occurs naturally in flaky skin mice (fsn/fsn). Affected mice are normal at birth, except for a hypochromic anemia. Subsequently, they develop hyperkeratotic plaques and acanthosis with elongation of rete ridges. Scanning electron microscopic examination revealed a greatly thickened epidermis, a sparsity of hairs and scale accumulations on the epidermal surface. Hair shafts had conspicuous pits, striations, and exophytic protrusions. Nails were bent at a 90 degrees angle with surface irregularities and accumulations of scale at the nail base. Transmission electron microscopic examination showed increased epidermal thickness, mitochondrial aberrations, and intraepidermal invasion by neutrophils. Keratohyalin abnormalities were detected using immunocytochemical staining for profilaggrin. At the dermal-epidermal junction, numerous macrophages and mast cells were seen in close proximity to focal dissolutions of the basement membrane. A high density of collagen fibers and cellular infiltrates were evident in the papillary dermis. This constellation of ultrastructural aberrations is typically found in psoriasis vulgaris and supports the theory that the flaky skin mouse mutation is a naturally occurring analog to one variety of human psoriasis vulgaris.

Ankylosing enthesitis, dactylitis, and onychoperiostitis in male DBA/1 mice: a model of psoriatic arthritis. Lories R J U,Matthys P,de Vlam K,Derese I,Luyten F P Annals of the rheumatic diseases OBJECTIVES:To further characterise spontaneous arthritis in aging male DBA/1 mice as a model of spondyloarthropathy and psoriatic arthritis with particular attention to signs of inflammation and nail involvement. MATERIALS AND METHODS:Aging male DBA/1 mice from different litters were caged together (4-6 mice per cage) at the age of 12 weeks, checked twice a week for signs of arthritis, and killed at different times. Hind paws were dissected and processed for histology. RESULTS:Disease incidence varied between 50% and 100% in four different experiments. Besides clinical signs of arthritis, nail abnormalities were noticed. Pathological examination showed the occurrence of dactylitis characterised by diffuse neutrophil infiltration in 6 of 50 paws examined. Onycho-periostitis with progressive destruction of the nail bed and the underlying distal phalanx was seen in 5 of 50 paws examined. CONCLUSIONS:Although dactylitis and onychoperiostitis are rare manifestations of the disease process, these data strongly suggest that spontaneous arthritis in aging male DBA/1 mice shares important features with human psoriatic arthritis. This model may therefore be an important tool to study links between stress, sex, inflammation, and new bone formation with particular relevance to human psoriatic arthritis. 10.1136/ard.2003.013599

Mice lacking endogenous major histocompatibility complex class II develop arthritis resembling psoriatic arthritis at an advanced age. Bárdos Tamás,Zhang Jian,Mikecz Katalin,David Chella S,Glant Tibor T Arthritis and rheumatism OBJECTIVE:To describe and characterize a novel inflammatory toe disease with severe bone destruction that developed spontaneously in "humanized" (HLA transgenic) mice lacking their own major histocompatibility complex (MHC). METHODS:We studied 5 different HLA transgenic mouse lines (HLA-DR2.Ab(0), DR3.Ab(0), DR4.Ab(0), DQ6.Ab(0), and DQ8.Ab(0)) in similar genetic background for an extended period of time (>14 months). Clinical, radiologic, and histologic abnormalities were monitored, and the MHC-related major immunologic parameters in affected and resistant mice were compared. RESULTS:Animals of 4 transgenic lines (HLA-DR2.Ab(0), DR4.Ab(0), DQ6.Ab(0), and DQ8.Ab(0)) developed severe toe inflammation accompanied by progressive bone resorption, hyperkeratosis, alopecia, loss of nails, and shortening and thickening of the distal phalanges. HLA-DR3.Ab(0) transgenic mice were resistant to inflammation. The disease manifested only at advanced ages (6 months or older) and affected 70-100% of the mice, with a female preponderance. The clinical signs and the radiographic and histopathologic features of the affected toes were not similar to those of any disease previously described in mice but did resemble those described for human psoriatic arthritis (PsA). Mice from the 4 susceptible lines expressed lower levels of the HLA transgene and exhibited significantly fewer CD4+ cells in the peripheral blood and reduced natural killer cell activity compared with mice from the resistant HLA-DR3.Ab(0) line. CONCLUSION:This novel, spontaneously developing PsA-like toe disease in MHC-manipulated mice seems to be related to the absence of endogenous MHC class II. Replacement with HLA transgene expression that is insufficient (or no replacement at all) may result in imbalanced MHC class I and class II functions and lead to development of the disease. 10.1002/art.10637