BATTEN-DISEASE AND THE ATP SYNTHASE SUBUNIT-C TURNOVER PATHWAY - RAISING ANTIBODIES TO SUBUNIT-C

Analysis of storage bodies in the ceroid-lipofuscinoses (Batten diseas e) has demon strated a high protein content suggestive of a proteinosi s. Direct N-terminal sequencing has shown that subunit c of mitochondr ial ATP synthase is specifically stored in the disease in sheep and ca ttle, and in the human late infantile and juvenile diseases, as well a s in 3 breeds of dogs, No differences have been found between the stor ed subunit c and that in normal mitochondria, No other mitochondrial c omponents are stored, Different proteins, sphingolipid activator prote ins (SAPs or saposins) A and D, are stored in the infantile disease. L inkage studies have shown that different forms of ceroid-lipofuscinosi s are coded for on different genes on different chromosomes, The genes for subunit c, its production, its insertion into mitochondria, and m itochondrial function are normal, This suggests that underlying the va rious forms of the disease is a family of lesions in the normal pathwa y of subunit c turnover, after its normal insertion into the ATP synth ase complex. Antibodies to subunit c offer one way of mapping that pat hway and detecting the sites of lesions, Specific antibodies have been raised against stored subunit c, using a liposomal adjuvant system wh ich proved superior to classical adjuvants, These antibodies are also useful diagnostically, both in Western blotting and in immunocytochemi stry. (C) 1995 Wiley-Liss, Inc.