Palmer D N, Bayliss S L, Westlake V J
Centre for Molecular Biology, Lincoln University, Canterbury, New Zealand.
Am J Med Genet. 1995 Jun 5;57(2):260-5. doi: 10.1002/ajmg.1320570230.
Analysis of storage bodies in the ceroid-lipofuscinoses (Batten disease) has demonstrated a high protein content suggestive of a proteinosis. Direct N-terminal sequencing has shown that subunit c of mitochondrial ATP synthase is specifically stored in the disease in sheep and cattle, and in the human late infantile and juvenile diseases, as well as in 3 breeds of dogs. No differences have been found between the stored subunit c and that in normal mitochondria. No other mitochondrial components are stored. Different proteins, sphingolipid activator proteins (SAPs or saposins) A and D, are stored in the infantile disease. Linkage studies have shown that different forms of ceroid-lipofuscinosis are coded for on different genes on different chromosomes. The genes for subunit c, its production, its insertion into mitochondria, and mitochondrial function are normal. This suggests that underlying the various forms of the disease is a family of lesions in the normal pathway of subunit c turnover, after its normal insertion into the ATP synthase complex. Antibodies to subunit c offer one way of mapping that pathway and detecting the sites of lesions. Specific antibodies have been raised against stored subunit c, using a liposomal adjuvant system which proved superior to classical adjuvants. These antibodies are also useful diagnostically, both in Western blotting and in immunocytochemistry.
对蜡样脂褐质沉积症（巴滕病）中储存小体的分析表明，其蛋白质含量很高，提示存在蛋白沉积症。直接N端测序显示，线粒体ATP合酶亚基c在绵羊和牛的该病、人类晚发性婴儿型和青少年型疾病以及3种犬类品种中特异性储存。储存的亚基c与正常线粒体中的亚基c之间未发现差异。未储存其他线粒体成分。不同的蛋白质，即鞘脂激活蛋白（SAPs或鞘磷脂激活蛋白）A和D，在婴儿型疾病中储存。连锁研究表明，不同形式的蜡样脂褐质沉积症由不同染色体上的不同基因编码。亚基c的基因、其产生、插入线粒体以及线粒体功能均正常。这表明，在各种形式的疾病背后，是亚基c正常插入ATP合酶复合物后，其正常周转的正常途径中的一系列病变。针对亚基c的抗体提供了一种绘制该途径并检测病变部位的方法。使用脂质体佐剂系统产生了针对储存的亚基c的特异性抗体，该系统被证明优于传统佐剂。这些抗体在蛋白质印迹法和免疫细胞化学中也具有诊断用途。
