Yamakoshi Yasuo, Hu Jan C C, Liu Shengxi, Sun Xiaoling, Zhang Chuhua, Oida Shinichiro, Fukae Makato, Simmer James P
University of Texas School of Dentistry, Health Science Center at San Antonio, Department of Pediatric Dentistry, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
Connect Tissue Res. 2002;43(2-3):167-75. doi: 10.1080/03008200290001131.
Mucopolysaccharidosis type IVA (Morquio A syndrome, MPS IVA) is a rare, autosomal recessive disorder with a prevalence of 1 in 170,000 live births. It is caused by a deficiency of N-acetylgalactosamine 6-sulfatase (GALNS), a lysosomal hydrolase encoded by a gene on human chromosome 16q24.3. Mucopolysaccharidosis type IVA is the only known MPS that is associated with structural defects in dental enamel. GALNS cleaves the sulfate group from N-acetylgalactosamine 6-sulfate and galactose 6-sulfate, which are specifically found in keratan sulfate and chondroitin 6-sulfate. A pathologic absence of GALNS activity results in the accumulation of these glycosaminoaglycans in the urine and in the lysosomes of tissues that turn them over. There is currently no animal model for MPS IVA. To learn more about how a GALNS deficit could lead to enamel defects, we have cloned and characterized a full-length pig GALNS cDNA. GALNS mRNA was localized in developing teeth by in situ hybridization, Northern blot, and reverse-transcription polymerase chain reaction analyses, while GALNS substrates were localized using immunohistochemistry. We report that secretory ameloblasts were positive for GALNS mRNA, as well as for keratan sulfate and chondroitin 6-sulfate. We conclude that enamel defects associated with the loss of GALNS activity in persons with MPS IVA are likely to result from the pathological accumulation of keratan sulfate and chondroitin 6-sulfate in the lysosomes of secretory stage ameloblasts.
IVA型黏多糖贮积症（莫尔基奥A综合征，MPS IVA）是一种罕见的常染色体隐性疾病，活产婴儿中的患病率为1/170,000。它是由N - 乙酰半乳糖胺6 - 硫酸酯酶（GALNS）缺乏引起的，GALNS是一种溶酶体水解酶，由人类染色体16q24.3上的一个基因编码。IVA型黏多糖贮积症是唯一已知的与牙釉质结构缺陷相关的黏多糖贮积症。GALNS从N - 乙酰半乳糖胺6 - 硫酸盐和半乳糖6 - 硫酸盐上切割硫酸基团，这两种物质在硫酸角质素和硫酸软骨素6 - 硫酸盐中特异性存在。GALNS活性的病理性缺失导致这些糖胺聚糖在尿液中以及在对其进行代谢的组织溶酶体中积累。目前尚无IVA型黏多糖贮积症的动物模型。为了更多地了解GALNS缺乏如何导致牙釉质缺陷，我们克隆并鉴定了全长猪GALNS cDNA。通过原位杂交、Northern印迹和逆转录聚合酶链反应分析将GALNS mRNA定位在发育中的牙齿中，同时使用免疫组织化学定位GALNS底物。我们报告分泌性成釉细胞对GALNS mRNA以及硫酸角质素和硫酸软骨素6 - 硫酸盐呈阳性。我们得出结论IVA型黏多糖贮积症患者中与GALNS活性丧失相关的牙釉质缺陷可能是由于分泌期成釉细胞溶酶体中硫酸角质素和硫酸软骨素6 - 硫酸盐的病理性积累所致。
