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首页> 外文期刊>Genomics >Canine heparan sulfate sulfamidase and the molecular pathology underlying Sanfilippo syndrome type A in Dachshunds.
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Canine heparan sulfate sulfamidase and the molecular pathology underlying Sanfilippo syndrome type A in Dachshunds.

机译：腊肠犬硫酸乙酰肝素磺酰胺酶和桑菲利波综合征A型潜在的分子病理学。

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摘要

Heparan sulfate sulfamidase (HSS) is a lysosomal exohydrolase that, when deficient, results in intralysosomal accumulation of heparan sulfate and the clinical phenotype of Sanfilippo syndrome type A. The first animal disease homolog of human Sanfilippo syndrome type A has been recently indentified in Dachshund littermates. To identify the molecular defect, the nucleotide sequences of the normal canine HSS gene and cDNA were determined using PCR-based approaches. The coding region showed 87% nucleotide homology, and 89% amino acid sequence homology, with human HSS. All exon-intron borders were conserved. Sequence analysis of the entire coding region with exon-intron boundaries was performed in the propositus, a healthy littermate, and six unrelated normal dogs. Comparison revealed a 3-bp deletion, 737-739delCCA, resulting in the loss of threonine at position 246 in both alleles of the propositus and in one allele of a healthy littermate. Prediction of the three-dimensional structure of canine HSS, based on homology with human arylsulfatases A and B, suggested the pathogenic effect of this deletion. Six other sequence variations in exons, and 10 in introns, appear to be benign polymorphisms. This study supports the potential development of a canine model of Sanfilippo syndrome type A to evaluate gene therapy for this disorder. Copyright 2000 Academic Press.
机译：硫酸乙酰肝素磺酰胺酶（HSS）是一种溶酶体外水解酶，缺乏时会导致溶酶体内硫酸肝素的积累和Sanfilippo综合征A型的临床表型。最近在达克斯猎犬同窝幼仔中发现了人类Sanfilippo综合征A型的第一个动物疾病同源物。 。为了鉴定分子缺陷，使用基于PCR的方法确定了正常犬HSS基因和cDNA的核苷酸序列。编码区与人HSS显示出87％的核苷酸同源性和89％的氨基酸序列同源性。所有外显子-内含子边界均被保留。对有外显子-内含子边界的整个编码区的序列进行了分析，其中有一个个体，一只健康的同窝幼犬和六只无关的正常狗。比较结果显示，缺失3-bp，即737-739delCCA，导致在性命中的两个等位基因和健康同窝的一个等位基因中第246位的苏氨酸丢失。基于与人芳基硫酸酯酶A和B的同源性，对犬HSS三维结构的预测表明了这种缺失的致病作用。外显子的其他六个序列变异和内含子的其他十个变异似乎是良性多态性。这项研究支持建立A型Sanfilippo综合征犬模型以评估该疾病的基因治疗的潜在发展。版权所有2000学术出版社。

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