Ray J, Bouvet A, DeSanto C, Fyfe J C, Xu D, Wolfe J H, Aguirre G D, Patterson D F, Haskins M E, Henthorn P S
James A. Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
Genomics. 1998 Mar 1;48(2):248-53. doi: 10.1006/geno.1997.5189.
Mucopolysaccharidosis type VII (MPS VII) is an inherited disease resulting from deficient activity of the lysosomal acid hydrolase beta-glucuronidase (GUSB) and has been reported in humans, mice, cats, and dogs. To characterize canine MPS VII, we have isolated and sequenced the canine GUSB cDNA from normal and affected animals. A single nucleotide substitution was detected in the GUSB cDNA derived from MPS VII dogs. This guanosine to adenine base change at nucleotide position 559 in the canine cDNA sequence causes an arginine to histidine substitution at amino acid position 166. Introduction of the G to A substitution at position 559 in a mammalian expression vector containing the normal canine GUSB cDNA nearly eliminated the GUSB enzymatic activity, demonstrating that this mutation is the cause of canine MPS VII. A retroviral vector expressing the full-length canine beta-glucuronidase cDNA corrected the deficiency in MPS VII cells.
黏多糖贮积症VII型（MPS VII）是一种由溶酶体酸性水解酶β-葡萄糖醛酸酶（GUSB）活性不足导致的遗传性疾病，已在人类、小鼠、猫和狗中报道。为了表征犬类MPS VII，我们从正常和患病动物中分离并测序了犬类GUSB cDNA。在源自MPS VII犬的GUSB cDNA中检测到一个单核苷酸替换。犬cDNA序列中第559位核苷酸的这种鸟嘌呤到腺嘌呤的碱基变化导致第166位氨基酸处的精氨酸被组氨酸替换。在含有正常犬GUSB cDNA的哺乳动物表达载体中，第559位的G到A替换几乎消除了GUSB酶活性，表明该突变是犬类MPS VII的病因。表达全长犬β-葡萄糖醛酸酶cDNA的逆转录病毒载体纠正了MPS VII细胞中的缺陷。
