Clinicopathological Phenotype of Autosomal Recessive Cholesterol Deficiency in Holstein Cattle

Mock, T.; Mehinagic, K.; Menzi, F.; Studer, E.; Oevermann, A.; Stoffel, M.H.; Drögemüller, C.; Meylan, M.; Regenscheit, N.

The small intestine of all animals was diffusely filled with a moderate amount of bright yellow, beige to limegreen, liquid, and partially foamy to fatty content (Fig 2A) . The mucosa of the distal two thirds of the small intestine was severely edematous and appeared whitish (Fig 2A) . The large intestine was filled with a yellow to green liquid with a partially foamy to fatty content, consistent with steatorrhea. The rectal contents of calf no. 1 and the heifer (no. 6) appeared less liquid than those from calves no. 2-5. Histological changes were most prominent in the small intestine and accentuated in the jejunum in all animals. The enterocytes covering the tips of the villi contained large amounts of optically empty, round to oval vacuoles, ranging from 2 to 20 lm in diameter ( Fig 2B) . Multifocally, the nuclei of the affected enterocytes were displaced to the basal cell borders. In frozen sections, these intracytoplasmic vacuoles and large parts of the intestinal content were positively stained by Sudan stain indicating lipid origin (Fig 2B) . Furthermore, multiple lacteals were moderately to severely dilated, correlating with the macroscopically visible edema. No pathomorphological or pathohistological lesions were observed in the liver. Transmission electron microscopy (TEM) corroborated the presence of large intracytoplasmic lipid droplets in the small intestinal enterocytes. The droplets filled most of the supranuclear cytoplasm but also occurred in an infranuclear position ( Fig 2C) . In other respects, organelles and intercellular spaces were typical. Furthermore, isolated lipid droplets were seen in hepatocytes but to a minor extent as compared with the enterocytes, excluding a hepatic steatosis on TEM level. Histologically, single dilated myelin sheaths containing fragmented axons and macrophages without any particular distribution pattern were observed in the central nervous system (CNS) of the heifer. The variation of nerve fiber size and the proportion of small nerve fibers appeared to be increased in the sciatic nerve of the heifer, compared to a control animal of the same age (Fig 2D) . Myelin sheaths of numerous axons were decreased in thickness and, multifocally, hypertrophied Schwann cells enclosed the myelin sheaths. In the eyes, no retinal degeneration was present.