Age-related accumulation of ceroid-like pigment in mice with Chediak-Higashi syndrome

The Chediak-Higashi Syndrome (CHS) is a rare inherited disorder occurring in man and several animal homologs including the beige mouse; it is characterized by pigmentary dilution, susceptibility to pyogenic infections, and the presence of enlarged lysosomes in many cell types. Beige mice 6 months of age and older were found to have darkened livers, kidneys, and spleens, accompanied by splenomegaly. A fluorescence microscopic survey of tissues from beige mice revealed marked accumulations of a microscopic survey of tissues from beige mice revealed marked accumulations of a yellow autofluorescent pigment inhepatocytes, renal proximal tubule cells, and splenic macrophages. Additionally, large amounts of hemosiderin were present in the spleen. In beige mice, the pigment was noted in animals as young as 1 to 2 weeks of age and gradually increased in amount as the animals aged. A histochemical investigation of the pigment showed that it was ceroid-like in nature and contained in lysosomes. Ultrastructurally, the pigment was composed of lipid-like droplets embedded in a dense matrix and surrounded by a limiting membrane. The accumulation of ceroid-like material in beige mice may be a reflection of the metabolic disturbance which underlies CHS.