Palmer D N, Fearnley I M, Medd S M, Walker J E, Martinus R D, Bayliss S L, Hall N A, Lake B D, Wolfe L S, Jolly R D
Department of Veterinary Pathology and Public Health, Massey University, Palmerston North, New Zealand.
Adv Exp Med Biol. 1989;266:211-22; discussion 223. doi: 10.1007/978-1-4899-5339-1_15.
The ceroid lipofuscinoses (Batten's disease) are a group of neuro-degenerative lysosomal storage diseases of children and animals that are recessively inherited. In the diseased individuals fluorescent storage bodies accumulate in a wide variety of cells, including neurons. The material stored in the cells of sheep affected with ceroid lipofuscinosis is two-thirds protein. The stored material does not arise from lipid peroxidation or a defect in lipid metabolism, and the lipid content is consistent with a lysosomal origin for the storage bodies. The major protein stains poorly with Coomassie blue dye and is soluble in organic solvents. It has an apparent molecular weight of 3,500 and its amino acids sequence is identical to that of the dicyclohexylcarbodiimide (DCCD) reactive proteolipid, subunit c, of mammalian mitochondrial ATP synthases. Apart from removal of mitochondrial import sequences, it has not been modified post-translationally. At least 50% of the mass of the storage bodies is composed of this protein. A minor protein sequence related to the 17-kDa subunit of vacuolar H(+)-ATPase is also found in storage bodies isolated from pancreas. As in humans and cattle, the ovine protein is the product of two expressed genes named P1 and P2. In normal and diseased animals there are no differences in sequences between P1 cDNAs or P2 cDNAs, nor do levels of mRNAs in liver for P1 or P2 differ substantially between normal and diseased animals. Both normal and diseased sheep also express a spliced pseudogene encoding amino acids 1 to 31 of the mitochondrial import presequence. The peptides they encode differ by one amino acid; arginine-23 is changed to glutamine in the diseased sheep. Storage bodies isolated from brains and pancreas of children affected with the juvenile and late infantile forms of ceroid lipofuscinosis also contain large amounts of material that is identical to subunit c of ATP synthase. However, the protein is not present in storage bodies isolated from brains of patients affected with the infantile form of the disease, and these storage bodies contain other unidentified proteins. It is possible that the cause of ovine, juvenile and late infantile ceroid lipofuscinoses is related to a defect in degradation of the subunit c of mitochondrial ATP synthase.
蜡样脂褐质沉积症（巴滕病）是一组儿童和动物的神经退行性溶酶体贮积病，呈隐性遗传。在患病个体中，荧光贮积体在包括神经元在内的多种细胞中积累。患蜡样脂褐质沉积症的绵羊细胞中储存的物质有三分之二是蛋白质。储存的物质并非源于脂质过氧化或脂质代谢缺陷，且脂质含量与贮积体的溶酶体起源一致。主要蛋白质用考马斯亮蓝染料染色效果不佳，且可溶于有机溶剂。其表观分子量为3500，氨基酸序列与哺乳动物线粒体ATP合酶的二环己基碳二亚胺（DCCD）反应性蛋白脂质亚基c相同。除了去除线粒体导入序列外，它在翻译后未被修饰。至少50%的贮积体质量由这种蛋白质组成。在从胰腺分离的贮积体中还发现了一种与液泡H(+) - ATP酶17 kDa亚基相关的次要蛋白质序列。与人类和牛一样，绵羊的这种蛋白质是两个名为P1和P2的表达基因的产物。在正常和患病动物中，P1 cDNA或P2 cDNA之间的序列没有差异，正常和患病动物肝脏中P1或P2的mRNA水平也没有显著差异。正常和患病绵羊还都表达一种剪接假基因，该假基因编码线粒体导入前序列的第1至31个氨基酸。它们编码的肽相差一个氨基酸；患病绵羊中精氨酸-23变为谷氨酰胺。从患有青少年型和晚期婴儿型蜡样脂褐质沉积症的儿童的大脑和胰腺中分离出的贮积体也含有大量与ATP合酶亚基c相同的物质。然而，在患有婴儿型疾病的患者大脑中分离出的贮积体中不存在这种蛋白质，这些贮积体含有其他未鉴定的蛋白质。绵羊、青少年型和晚期婴儿型蜡样脂褐质沉积症的病因可能与线粒体ATP合酶亚基c的降解缺陷有关。
