Shull R M, Hastings N E, Selcer R R, Jones J B, Smith J R, Cullen W C, Constantopoulos G
J Clin Invest. 1987 Feb;79(2):435-43. doi: 10.1172/JCI112830.
Five dogs with mucopolysaccharidosis I, a model of human Hurler/Scheie syndrome, were transplanted with marrow from phenotypically normal littermates at 5 mo of age. At 3 and 9 mo posttransplantation, biopsies of cerebral cortex, liver, and cerebrospinal fluid were obtained. The alpha-L-iduronidase levels in these tissues were 0.8-7.4, 26-45, and 6.3-14.9% of the paired donor tissues, respectively. Although iduronidase was present in relatively low levels in the recipients' brains and cerebrospinal fluid at both biopsy times, reduction in brain glycosaminoglycan (GAG) was comparable to that observed in liver. Ultrastructural studies of cells within the transplanted dogs' brains showed less lysosomal distension and storage product than in affected, nontransplanted, littermate controls. The most marked clearing of stored GAG was in cells surrounding blood vessels, but decreased lysosomal storage in neurons and glial cells was also observed. Urinary GAG excretion also decreased to near normal levels by 5 mo posttransplantation.
五只患有黏多糖贮积症 I 型（人类Hurler/Scheie综合征的模型）的犬在5月龄时接受了来自表型正常同窝仔犬的骨髓移植。在移植后3个月和9个月，获取了大脑皮质、肝脏和脑脊液的活检样本。这些组织中的α-L-艾杜糖醛酸酶水平分别为配对供体组织的0.8 - 7.4%、26 - 45%和6.3 - 14.9%。尽管在两次活检时，受体的大脑和脑脊液中艾杜糖醛酸酶的水平相对较低，但大脑中糖胺聚糖（GAG）的减少与肝脏中观察到的情况相当。对移植犬大脑内细胞的超微结构研究显示，与受影响的、未移植的同窝对照犬相比，溶酶体扩张和储存产物减少。储存的GAG清除最明显的是在血管周围的细胞中，但在神经元和胶质细胞中溶酶体储存也减少。移植后5个月，尿GAG排泄也降至接近正常水平。
