A study of the biochemical and morphological changes in GM₂-gangliosidosis of Yorkshire swine and the influence of chloroquine HCL upon these changes

Abstract

The biochemical and morphological characteristics of porcine cerebrospinal lipodystrophy in different stages of development were ascertained and were compared to corresponding characteristics of the human GM₂-gangliosidoses. The study was divided into 2 separate experiments. In the 1st experiment 11 control (normal and carrier) and 14 affected Yorkshire pigs were used to investigate the pathogenesis of the fundamental cellular lesion by evaluating the progression of the basic biochemical (enzyme and ganglioside assays) and morphological (neuronal and glial) changes in the central nervous system. Tissues were collected from pigs killed at 1 day (newborn or stillborn) to 175 days of age. The purpose of the 2nd experiment was to evaluate the effect of chloroquine HCl on lipodystrophic pigs. Chloroquine HCl was given to 4 control and 4 affected pigs at the rate of 2.5 mh/Ib/day, and to 1 control and 1 affected pig at the rate of 7.5 to 10.0 mg/Ib every other day. Control and affected pigs used in each experiment were identified on the basis of the level of N-acetly-B-D-hexosaminidase activity in serum and in leukocyte, liver, and brain homogenates. Total N-acetyl-B-D-hexosaminidase values in the tissue homogenatcs were lower in affected than in control, while serum total N-acetyl-B-D-hexosaminidase levels were higher in the affected pigs than in either the carrier or normal pigs. The serum enzyme assay was found to be a reliable test to distinguish carrier pigs, with moderate serum levels of activity of this enzyme, from the normal pigs which had the lowest level of enzyme activity in the serum. Two consistent features of all affected pigs were the presence of diffuse grayish-white spots in the retinas examined either stereomicroscopically or ophthalmoscophically, and prominent granules in the cytoplasm of most neutrophils and lymphocytes stained with Wright-Giemsa stain..