The effect of tacrolimus hydrate (FK506) ointment on spontaneous dermatitis in NC/Nga (NC) mice was examined. FK506 ointment (0.1-1%) suppressed the development of dermatitis and was also therapeutically effective against established dermatitis. Increases in CD4-positive T cells (helper T cells), mast cells, eosinophils and immunostaining of interleukin (IL)-4, IL-5 and IgE were confirmed in the skin of the NC mice, and FK506 ointment suppressed all of these changes. Increased plasma IgE was also confirmed in the NC mice, and treatment with FK506 ointment reduced the plasma IgE level. These results suggested that FK506 suppressed the dermatitis by inhibiting the activation of inflammatory cells and by blocking the cytokine network in the skin of the NC mice. The commercially available steroid ointments showed only marginal effect on the development of dermatitis and showed some signs of side effects such as alopecia or atrophy of the skin. The effect of the steroids might have been masked by these side effects because the steroids showed similar inhibitory effects on the skin histopathological changes and the increase of plasma IgE. From these results, FK506 ointment can be expected to be a useful drug for atopic dermatitis.

No abstract

Background: Mast cell chymase is thought to participate in allergic inflammation, but its precise role remains undetermined. Inbred NC/Nga mice develop skin lesions similar to atopic dermatitis (AD) when they grow up in a conventional environment. To elucidate the possible role of chymase in AD, we examined the effect of a chymase inhibitor on skin lesions of NC/Nga mice. Methods: NC/Nga mice were given the chymase inhibitor SUN-C8257 daily at 150 mg/kg/day with drinking water, and the severity of the dermatitis was evaluated on day 35 of the experiment. The role of chymase in dermatitis was further investigated in vitro and in vivo using recombinant mouse mast cell protease-4 (mMCP-4). Results: Administration of SUN-C8257 significantly reduced the clinical skin and histological score in NC/Nga mice. SUN-C8257 also inhibited the accumulation of inflammatory cells, such as eosinophils and mast cells, in the affected lesions in this model. mMCP-4 stimulated eosinophil migration in vitro, and intradermal injection of the enzyme resulted in a significant accumulation of inflammatory cells, including eosinophils, at the injection site. Thus amelioration of the skin lesions in NC/Nga mice by SUN-C8257 might be, at least in part, due to the suppression of cell infiltration in the lesions. Conclusions: Mast cell chymase may contribute to the pathogenesis of AD, and SUN-C8257 will be beneficial to the treatment of the skin disorder.

Hereditary multiple malformation (HMM), a new mutation of Japanese quail (Coturnix japonica), is controlled by an autosomal recessive gene. The proposed gene symbol for the mutant gene is hmm. The majority of the homozygotes die at the sixth day of incubation, and the remainder die at various stages by 15 days of incubation. The homozygotes surviving to the late embryonic stage have greatly shortened lower and upper beaks that are set apart and show an early embryo-like body shape, with feather buds but no plumules. Furthermore, they show syndactylous polydactyly in both fore and hind limbs. In the abdomen of the homozygote, a part of the ventriculus, liver, and small intestine protrudes out of the umbilicus region. In the skeleton of the late HMM embryos, ossification is generally delayed and morphogenetic abnormalities are observed all over the body. This mutant seems to become a powerful animal model in the research fields for morphogenesis.

No abstract