Bastedo L, Sands M S, Lambert D T, Pisa M A, Birkenmeier E, Chang P L
Department of Biology, McMaster University, Hamilton, Ontario, Canada.
J Clin Invest. 1994 Sep;94(3):1180-6. doi: 10.1172/JCI117434.
The gusmps/gusmps mouse is a model of the human lysosomal storage disease mucopolysaccharidosis type VII caused by deficient beta-glucuronidase activity. Bone marrow transplantation has been shown to correct some of their biochemical and pathological abnormalities but its efficacy in correcting their neurological functional deficits is unknown. We transplanted the neonatal gusmps/gusmps mice and their normal controls and evaluated their central nervous system function with two behavioral tests: the grooming test, a developmentally regulated and genetically based activity, and a Morris water maze test which assessed spatial learning abilities. The two transplanted groups groomed less than the normals, were unable to remember the location of an invisible platform from day to day, and were severely impaired at developing strategies to locate the platform in unfamiliar locations. The performance of both normal and mutant transplanted groups was clearly inferior to the untreated normals and, in some instances, close to or worse than the untreated mutants, even though the enzyme abnormalities of the mutants have been partially corrected. Hence, the behavioral deficits in the mutant mice were not restored to normal while similarly treated normal mice showed significant functional deterioration, indicating the detrimental consequence of this therapy in the neonatal period.
gusmps/gusmps小鼠是一种人类溶酶体贮积病——VII型黏多糖贮积症的模型，该病由β-葡萄糖醛酸酶活性缺乏引起。骨髓移植已被证明可纠正其一些生化和病理异常，但其纠正神经功能缺陷的疗效尚不清楚。我们对新生的gusmps/gusmps小鼠及其正常对照进行了移植，并通过两项行为测试评估它们的中枢神经系统功能：梳理测试，一种受发育调节且基于基因的活动，以及莫里斯水迷宫测试，该测试评估空间学习能力。两个移植组的梳理行为少于正常组，无法日复一日地记住不可见平台的位置，并且在制定在不熟悉位置定位平台的策略方面严重受损。正常和突变移植组的表现明显低于未治疗的正常组，在某些情况下，甚至接近或差于未治疗的突变组，尽管突变体的酶异常已得到部分纠正。因此，突变小鼠的行为缺陷并未恢复正常，而同样接受治疗的正常小鼠却出现了明显的功能恶化，这表明这种治疗在新生儿期具有有害后果。
