Somatic cell genetic analysis of the galactocerebrosidase gene: lack of complementation in human Krabbe disease/twitcher mouse cell hybrids.
Somatic cell genetic analysis of the galactocerebrosidase gene: lack of complementation in human Krabbe disease/twitcher mouse cell hybrids.
复制标题
半乳糖脑苷酶基因的体细胞遗传分析：人克拉伯病/抽搐小鼠细胞杂交体缺乏互补。
DOI：
10.1002/jnr.490270406
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发表时间：
1990
影响因子：
4.2
通讯作者：
Raghavan,S
中科院分区：
文献类型：
--
作者：
Skiba,MC;Lyerla,TA;Konola,JT;Raghavan,S
半乳糖神经酰胺β-半乳糖苷酶(E.C.3.2.1.46：半乳糖脑苷酶)活性的遗传缺陷导致人类(克拉贝病)和小鼠(Twitcher突变体)的脑白质营养不良。为了确定Krabbe患者的细胞是否补充抽动细胞，在杂交组合中产生比缺乏半乳糖苷酶活性水平更高的半乳糖-脑苷酶活性，我们在一个已建立的Twitcher鼠细胞系与来自无关Krabbe病患者的五个细胞株之间进行了五个单独的杂交。从所有这些杂交中培育出的57个Twitcher小鼠/Krabbe体细胞杂交系，尽管存在人类14或17号染色体，但仍缺乏半乳脑苷酶活性，此前已有证据表明这些染色体携带半乳脑苷酶基因。Twitcher小鼠/阳性对照人成纤维细胞之间的对照杂交导致21个独立的杂交系中有14个表达高于不足水平的半乳杆菌溴化酶活性。Krabbe病患者和Twitcher突变小鼠细胞之间缺乏互补性提供了进一步的证据，证明Twitcher小鼠是真正的Krabbe病小鼠模型，并支持这两个物种的突变位于半乳糖脑苷酶结构基因内的假设。
The inherited deficiency of galactosylceramide β‐galactosidase (E.C. 3.2.1.46: galactocerebrosidase) activity results in globoid cell leukodystrophy in humans (Krabbe disease) and in mice (twitcher mutant). To determine whether Krabbe patients, cells complement twitcher cells to produce, in hybrid combination, greater than deficient levels of galacto‐cerebrosidase activity, five separate crosses were made between an established twitcher mouse cell line and five cell strains from unrelated Krabbe disease patients. A total of 57 twitcher mouse/Krabbe somatic cell hybrid lines developed from all of these crosses were deficient in galactocerebrosidase activity despite the presence of human chromosomes 14 or 17, which have been previously implicated as bearing the galactocerebrosidase gene. A control cross between twitcher mouse/positive control human fibroblasts resulted in 14 of 21 independent hybrid lines that expressed higher than deficient levels of galactocere brosidase activity. The lack of complementation between Krabbe disease patient and twitcher mutant mouse cells provides further evidence that the twitcher mouse is an authentic murine model for Krabbe disease and supports the hypothesis that the mutations in both species are within the structural gene for the galactocerebrosidase enzyme.