Hyaluronidase 3 (HYAL3) knockout mice do not display evidence of hyaluronan accumulation
Hyaluronidase 3 (HYAL3) knockout mice do not display evidence of hyaluronan accumulation
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DOI：
10.1016/j.matbio.2008.07.006
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发表时间：
2008-10-01
期刊：
影响因子：
6.9
通讯作者：
Triggs-Raine, Barbara
中科院分区：
文献类型：
--
作者：
Atmuri, Vasantha;Martin, Dianna C.;Triggs-Raine, Barbara
透明质酸酶是一种内切糖苷酶，可引起透明质酸(HA)的分解，透明质酸是脊椎动物细胞外基质中丰富的成分。在人类中，已在染色体3p21.3(Hyal2-HYAL1-HYAL3)和7q31.3(SPAM1-HYAL4-HYALP1)上发现了6个编码透明质酸酶样序列的平行基因。其中一个基因的突变。HYAL1，在1例粘多糖病(MPS)IX患者中报道。尽管HA分布广泛，但HYAL1缺陷患者表现出轻微的表型，这表明其他透明质酸酶家族成员参与了结构性HA的降解。建立了Hyal3基因敲除(Hyal3(-/-))小鼠，以确定HYAL3是否在结构性HA降解中起作用。Hyal3(-/-)小鼠存活、生育，并且没有表现出明显的表型变化。Hyal3(-/-)小鼠的X射线分析、关节组织学检查、全身重量、器官重量和血清HA水平均正常。在分析的透明蛋白3(-/-)组织中，没有发现糖胺聚糖积累的证据，包括空泡化。值得注意的是，在12-14个月龄的Hyal3(-/-)小鼠身上发现的唯一不同之处是肺组织切片中肺泡结构和细胞外基质厚度的细微变化。我们得出结论，HYAL3在结构性HA降解过程中不起主要作用。皇冠版权所有(C)2008由爱思唯尔出版。保留所有权利。
Hyaluronidases are endoglycosidases that initiate the breakdown of hyaluronan (HA), an abundant component of the vertebrate extracellular matrix. In humans, six paralogous genes encoding hyaluronidase-like sequences have been identified on human chromosomes 3p21.3 (HYAL2-HYAL1-HYAL3) and 7q31.3 (SPAM1-HYAL4-HYALP1). Mutations in one of these genes. HYAL1, were reported in a patient with mucopolysaccharidosis (MPS) IX. Despite the broad distribution of HA, the HYAL1-deficient patient exhibited a mild phenotype, suggesting other hyaluronidase family members contribute to constitutive HA degradation. Hyal3 knockout (Hyal3(-/-)) mice were generated to determine if HYAL3 had a role in constitutive HA degradation. Hyal3(-/-) mice were viable, fertile, and exhibited no gross phenotypic changes. X-ray analysis, histological Studies of joints, whole-body weights, organ weights and the serum HA levels of Hyal3(-/-) mice were normal. No evidence of glycosaminoglycan accumulation, including vacuolization, was identified in the Hyal3(-/-) tissues analyzed. Remarkably, the only difference identified in Hyal3(-/-) mice was a subtle change in the alveolar structure and extracellular matrix thickness in lung-tissue sections at 12-14 months-of-age. We conclude that HYAL3 does not play a major role in Constitutive HA degradation. Crown Copyright (C) 2008 Published by Elsevier B.V. All rights reserved.