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 fat ty acids. The morphological features of carnitine deficiency were stud ied in juvenile visceral steatosis (JVS) mice with congenital carnitin e deficiency. Untreated young mice showed marked hepatomegaly associat ed with fatty liver. In contrast, cardiac hypertrophy and systemic cir culatory impairment were the main findings in adult and aged mice with carnitine treatment. The principal lesions common to homozygous mutan t mice consisted of the following: 1) accumulation of fat droplets in various kinds of cells (hepatocytes, renal tubular epithelial cells, s alivary gland ductal cells, Brunner's gland epithelial cells, brown fa t cells, cardiac muscle fibers and striated muscle fibers in the thigh muscles, diaphragm and extrinsic muscle), 2) enlargement of hepatocyt es with infrequent hyaline globules in untreated young mice, 3) fine c ytoplasmic granules and hypertrophy of cardiac muscle fibers with biza rre nuclei, 4) atrophy of adrenocortical cells, 5) necrosis of lymphoc ytes in the thymic cortex and spleen, and 6) erosion or ulceration of the gastric mucosa. A wide variety of abnormalities in JVS mice, as re ported in humans with carnitine deficiency, strongly suggest the varia ble and complicated physiological role of carnitine in individual cell s or even in the same type of cell at different ages.