Time course of hepatic lipids accumulation in a strain of mice with an inherited deficiency of sphingomyelinase

Abstract

Sphingomyelinosis (gene symbol, spm) is a recessive autosomal mutation in mice that causes a condition analogous to the human disease known as Niemann-Pick disease. The time course of hepatic lipids accumulation in this murine model was investigated. Hepatosplenomegaly in spm/ spm mice was noticeable as early as 4 weeks of age, and reached its maximum level at 6 weeks of age. Thereafter the weights of liver and spleen decreased in parallel with a decrease in body weight and an increase in severity of neurological symptoms. Hepatic concentrations of unesterified cholesterol and sphingomyelin were considerably elevated by 4 weeks of age, and further increased linearly to the terminal stages of the disorder. Sphingomyelinase activities in the livers of spm/ + and +/+ mice showed normal adult levels from as early as 4 weeks of age, whereas the activity in spm/ spm mice was consistently 30-40 percent of the normal level from 4 to 12 weeks of age.