Tissue culture loading test with storage granules from animal models of neuronal ceroid-lipofuscinosis (Batten disease): testing their lysosomal degradability by normal and Batten cells.

Storage granules (SGs) from ovine and canine models of Batten disease were found to be easily phagocytosed by four cell types studied. The cell types tested were human fibroblasts and peripheral monocytes (control and from a late infantile Batten disease patient), rat C6 cell line, and neonatal cardiomyocytes. The phagocytosed SGs elicited an increase in acid phosphatase activity which was localized in the phagolysosome. After phagocytosis SGs were followed for various times ranging from 7 to 21 days and were found to be of unchanged density (phase contrast), autofluorescence, and ultrastructural appearance. These findings point to their undergradability, or very low degree of degradability, in phagolysosomes in both normal or Batten cultured cells. The Batten disease SGs are not toxic and did not cause any adverse affect on the host cells. Either the normal clearance rate from lysosomes is too slow to be measured by this technique or subunit c accumulation in lysosomes need not result from a primary lysosomal protease defect. Subunit c may aggregate, because of the lack of some normally preventive factor, resulting in a physical barrier to the degradation of this highly apolar molecule.