Michio Masuoka

Specific pathogen free conditions prevent transthyretin amyloidosis in mouse models

Transthyretin (TTR) associated amyloidosis is an autosomal dominant disorder characterized by peripheral and autonomic neuropathy. Both genetic and environmental factors are thought to be involved in development of TTR associated amyloidosis. Previously, we demonstrated that amyloid deposition was observed in various tissues of transgenic mouse lines carrying a human mutant TTR (Met30) gene. To analyze the influence of environmental factors on TTR amyloidosis, these amyloidogenic transgenic mouse models were kept under conventional (CV) or specific pathogen free (SPF) conditions. Although the serum levels of Met30 for mice housed in the CV and SPF conditions were similar, amyloid deposition was observed in CV conditions, but not in SPF conditions. In addition, the extent of amyloid deposition in transgenic mice was dependent on duration kept under CV conditions. There were significant differences in proportion of amyloid deposition in several tissues between CV and SPF conditions. Maintenance of these mice at 30°C did not induce amyloid deposition in SPF conditions. These results suggest that the SPF conditions can completely prevent amyloid deposition, and that environmental factors can affect the onset and progression even in a single gene disorder.

Effects of Fluoride on Developing Enamel and Dentin of Rat Incisors

Abstract The effects of fluoride on the developing enamel and dentin of rat incisors were investigated. Rats were treated orally with the anti-neoplastic agents, Tegafur and ethyl t-6-butoxy-5-fluorohexahydro-2, 4-dioxopyrimi-dine-r-5-carboxylate (TAC-278), and NaF at different doses for eight weeks. These anti-neoplastic agents contain fluorine (F) and appeared to release 5-fluorouracil after the treatment. Tegafur and TAC-278 induced mottled enamel characterized by pigment-free and chalky white areas. Histo-pathologically, ameloblasts, at the secretory to maturation stage, showed degeneration and necrosis, and formed a cystic irregular array. In the dentin, there were focal or diffuse hypoplastic defects resulting from degeneration and atrophy of odontoblasts. Microradiographically, calcio-traumatic lines resulting from damage to secretory ameloblasts, and calcio-traumatic zones resulting from damage to ameloblasts at the maturation stage were observed in the enamel. These changes were essentially the same as the abnormality resulting from NaF treatment. The F concentration in the incisors was highest in the NaF treated rats, and lowest in the TAC-278 treated rats. The severity of gross lesion of the incisors and the F concentration in the incisors were well correlated. From these results, it is suggested that, like NaF, an excessive dose of Tegafur or TAC-278 affects the developing enamel and dentin of rat incisors.