Sialidosis and galactosialidosis: chromosomal assignment of two genes associated with neuraminidase-deficiency disorders.
Sialidosis and galactosialidosis: chromosomal assignment of two genes associated with neuraminidase-deficiency disorders.
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唾液酸贮积症和半乳糖唾液酸贮积症：与神经氨酸酶缺乏症相关的两个基因的染色体分配。
DOI：
10.1073/pnas.83.6.1817
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发表时间：
1986
影响因子：
11.1
通讯作者：
Shows,TB
中科院分区：
文献类型：
--
作者：
Mueller,OT;Henry,WM;Haley,LL;Byers,MG;Eddy,RL;Shows,TB
遗传性人类疾病唾液酸沉积症和半乳糖唾液酸沉积症是糖蛋白特异性α-神经氨酸酶（酰基神经氨酸水解酶，EC 3.2.1.18;唾液酸酶）活性缺乏的结果。通过使用分离人类染色体的人-小鼠体细胞杂交，确定两个基因是表达神经氨酸酶所必需的。一组小鼠RAG-人杂交细胞证明了人神经氨酸酶的单基因需求，并允许将该基因分配到10号染色体的（pter----q23）区域。第二组小鼠胸苷激酶（TK）缺陷LM/TK-人杂交细胞证明，人神经氨酸酶活性需要染色体10和20都存在。分析小鼠RAG（次黄嘌呤/鸟嘌呤磷酸核糖转移酶缺陷）或LM/TK-细胞系与人唾液酸沉积症或半乳糖唾液酸沉积症成纤维细胞融合形成的种间杂交细胞或多核细胞中人神经氨酸酶表达表明RAG细胞系补充了半乳糖唾液酸沉积症缺陷，但LM/TK-细胞系没有。这消除了在RAG-人杂交细胞中对该基因的需求，并解释了这两个杂交组的不同染色体需求。缺乏10号或20号染色体的LM/TK-细胞杂交体（表型10+，20-和10-，20+）和神经氨酸酶缺陷的成纤维细胞的融合通过互补分析证实唾液酸沉积症是由10号染色体上的突变引起的，可能编码神经氨酸酶结构基因。半乳糖唾液酸沉积症是由位于20号染色体上的神经氨酸酶表达所需的第二个基因突变引起的。
The inherited human disorders sialidosis and galactosialidosis are the result of deficiencies of glycoprotein-specific alpha-neuraminidase (acylneuraminyl hydrolase, EC 3.2.1.18; sialidase) activity. Two genes were determined to be necessary for expression of neuraminidase by using human-mouse somatic cell hybrids segregating human chromosomes. A panel of mouse RAG-human hybrid cells demonstrated a single-gene requirement for human neuraminidase and allowed assignment of this gene to the (pter----q23) region of chromosome 10. A second panel of mouse thymidine kinase (TK)-deficient LM/TK- -human hybrid cells demonstrated that human neuraminidase activity required both chromosomes 10 and 20 to be present. Analysis of human neuraminidase expression in interspecific hybrid cells or polykaryocytes formed from fusion of mouse RAG (hypoxanthine/guanine phosphoribosyltransferase deficient) or LM/TK- cell lines with human sialidosis or galactosialidosis fibroblasts indicated that the RAG cell line complemented the galactosialidosis defect, but the LM/TK- cell line did not. This eliminates the requirement for this gene in RAG-human hybrid cells and explains the different chromosome requirements of these two hybrid panels. Fusion of LM/TK- cell hybrids lacking chromosome 10 or 20 (phenotype 10+,20- and 10-,20+) and neuraminidase-deficient fibroblasts confirmed by complementation analysis that the sialidosis disorder results from a mutation on chromosome 10, presumably encoding the neuraminidase structural gene. Galactosialidosis is caused by a mutation in a second gene required for neuraminidase expression located on chromosome 20.