An inversion of 25 base pairs causes feline GM2 gangliosidosis variant 0
An inversion of 25 base pairs causes feline GM2 gangliosidosis variant 0
复制标题
DOI：
10.1016/j.expneurol.2004.01.008
复制
发表时间：
2004-05-01
影响因子：
5.3
通讯作者：
Baker, HJ
中科院分区：
文献类型：
--
作者：
Martin, DR;Krum, BK;Baker, HJ
In G(M2) gangliosidosis variant 0, a defect in the beta-subunit of lysosomal beta-N-acetylhexosaminidase (EC 3.2.1.52) causes abnormal accumulation of G(M2) ganglioside and severe neurodegeneration.在家养短毛猫和呵叻猫中均描述了 G(M2) 神经节苷脂沉积症变体 0 的独特猫科动物模型。在这项研究中，我们确定家养短毛猫 G(M2) 神经节苷脂沉积症的致病突变是 β 亚基 (HEXB) 编码序列 3' 端的 25 个碱基对倒位，该倒位在蛋白质的羧基末端引入了 3 个氨基酸取代，并提前了 8 个氨基酸进行翻译终止。 25 碱基对倒位纯合猫的 β 亚基 mRNA 表达水平约为正常值的 190%，而蛋白质水平仅为正常值的 10-20%。由于25个碱基对的倒位与人类HEXB末端外显子的突变相似，因此家养短毛猫应该作为研究人类G(M2)神经节苷脂沉积症变体0（桑德霍夫病）分子发病机制的合适模型。 (C) 2004 Elsevier Inc. 保留所有权利。
In G(M2) gangliosidosis variant 0, a defect in the beta-subunit of lysosomal beta-N-acetylhexosaminidase (EC 3.2.1.52) causes abnormal accumulation of G(M2) ganglioside and severe neurodegeneration. Distinct feline models of G(M2) gangliosidosis variant 0 have been described in both domestic shorthair and Korat cats. In this study, we determined that the causative mutation of G(M2) gangliosidosis in the domestic shorthair cat is a 25-base-pair inversion at the extreme 3' end of the beta-subunit (HEXB) coding sequence, which introduces three amino acid substitutions at the carboxyl terminus of the protein and a translational stop that is eight amino acids premature. Cats homozygous for the 25-base-pair inversion express levels of beta-subunit mRNA approximately 190% of normal and protein levels only 10-20% of normal. Because the 25-base-pair inversion is similar to mutations in the terminal exon of human HEXB, the domestic shorthair cat should serve as an appropriate model to study the molecular pathogenesis of human G(M2) gangliosidosis variant 0 (Sandhoff disease). (C) 2004 Elsevier Inc. All rights reserved.