Heterogeneity of histopathologic features in the congenitally carnitine-deficient juvenile visceral steatosis (JVS) mouse

Carnitine is an essential cofactor for the oxidation of long-chain fatty acids. The morphological features of carnitine deficiency were studied in juvenile visceral steatosis (JVS) mice with congenital carnitine deficiency. Untreated young mice showed marked hepatomegaly associated with fatty liver. In contrast, cardiac hypertrophy and systemic circulatory impairment were the main findings in adult and aged mice with carnitine treatment. The principal lesions common to homozygous mutant mice consisted of the following: 1) accumulation of fat droplets in various kinds of cells (hepatocytes, renal tubular epithelial cells, salivary gland ductal cells, Brunner's gland epithelial cells, brown fat cells, cardiac muscle fibers and striated muscle fibers in the thigh muscles, diaphragm and extrinsic muscle), 2) enlargement of hepatocytes with infrequent hyaline globules in untreated young mice, 3) fine cytoplasmic granules and hypertrophy of cardiac muscle fibers with bizarre nuclei, 4) atrophy of adrenocortical cells, 5) necrosis of lymphocytes in the thymic cortex and spleen, and 6) erosion or ulceration of the gastric mucosa. A wide variety of abnormalities in JVS mice, as reported in humans with carnitine deficiency, strongly suggest the variable and complicated physiological role of carnitine in individual cells or even in the same type of cell at different ages.