EVIDENCE THAT LYSOSOMAL STORAGE OF PROTEOLIPIDS IS A CELL AUTONOMOUS PROCESS IN THE MOTOR-NEURON DEGENERATION (MND) MOUSE, A MODEL OF NEURONAL CEROID-LIPOFUSCINOSIS

The motor neuron degeneration (mnd) mouse has been documented to accum ulate proteolipid and thus is a model of neuronal ceroid lipofuscinosi s [Dunn, W.A., Raizada, M.K., Vogt, E.S. and Brown, E.A., Int. J. Dev. Neurosci., 12 (1994) 185-196; Faust, J.R., Rodman, J.S., Daniel, P.F. , Dice, J.F. and Bronson, R.T., J. Biol. Chem., 269 (1994) 10150-10155 ]. While accumulation of proteolipid in the hippocampus of chimeric mi ce composed of mnd and +/+ cells was found to be proportional to the c ontribution of mnd in the brain, accumulation within individual cells was the same for cells from chimeric and age-matched mnd mice. Bone ma rrow transplantation was used to altering the milieu of circulating fa ctors to determine whether this might modify the disease phenotype in mnd mice. Transplantation of bone marrow in neonatal or young mice did not reduce the age-associated accumulation of proteolipid within hipp ocampal neurons. The results of these experiments indicate that mnd re sults in a cell autonomous defect.