MURINE MUCOPOLYSACCHARIDOSIS TYPE-VII - CHARACTERIZATION OF A MOUSE WITH BETA-GLUCURONIDASE DEFICIENCY
MURINE MUCOPOLYSACCHARIDOSIS TYPE-VII - CHARACTERIZATION OF A MOUSE WITH BETA-GLUCURONIDASE DEFICIENCY
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DOI：
10.1172/jci114010
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发表时间：
1989-04-01
影响因子：
15.9
通讯作者：
WAWRZYNIAK, CJ
中科院分区：
文献类型：
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作者：
BIRKENMEIER, EH;DAVISSON, MT;WAWRZYNIAK, CJ
我们已经表征了一种新的突变小鼠，其实际上不具有β-葡萄糖醛酸酶活性。这种生物化学失败引起鼠溶酶体贮积病，其与人粘多糖样变性VII型（MPS VII; Sly综合征; β-淀粉样变性）具有许多有趣的相似性。葡萄糖醛酸酶缺乏症）。遗传分析表明，该突变作为常染色体隐性遗传，其定位于β-葡萄糖醛酸酶基因复合物，[Gus]，在染色体5的远端。尽管β-半乳糖苷酶活性降低> 200倍，Southern印迹分析未能检测到结构基因Gus-sb或17 kb的5“侧翼序列和4 kb的3”侧翼序列的任何异常。令人惊讶的是，灵敏的S1核酸酶测定表明，肾gusmps mRNA的相对水平通过增加apx正常地响应于雄激素诱导。11倍对这种突变小鼠的分析可能为人类MPS VII的发病机制提供有价值的信息，并为研究骨髓移植和基因转移治疗方法提供有用的系统。
We have characterized a new mutant mouse that has virtually no .beta.-glucuronidase activity. This biochemical defeat causes a murine lysosomal storage disease that has many interesting similarities to human mucopolysaccharidosis type VII (MPS VII; Sly syndrome; .beta.-glucuronidase deficiency). Genetic analysis showed that the mutation is inherited as an autosomal recessive that maps to the .beta.-glucuronidase gene complex, [Gus], on the distal end of chromosome 5. Although there is a > 200-fold reduction in the .beta.-glucuronidase mRNA concentration in mutant tissues, Southern blot analysis failed to detect any abnormalities in the structural gene, Gus-sb, or in 17 kb of 5'' flanking and 4 kb of 3'' flanking sequences. Surprisingly, a sensitive S1 nuclease assay indicated that the relative level of kidney gusmps mRNA responded normally to androgen induction by increasing .apprx. 11-fold. Analysis of this mutant mouse may offer valuable information on the pathogenesis of human MPS VII and provide a useful system in which to study bone marrow transplantation and gene transfer methods of therapy.