Dunnett S B, Carter R J, Watts C, Torres E M, Mahal A, Mangiarini L, Bates G, Morton A J
MRC Cambridge Centre for Brain Repair, University of Cambridge, London, United Kingdom.
Exp Neurol. 1998 Nov;154(1):31-40. doi: 10.1006/exnr.1998.6926.
Striatal grafts have been proposed as a potential strategy for striatal repair in Huntington's disease, but it is unknown whether the diseased brain will compromise graft survival. A transgenic mouse line has recently been described in which hemizygotes with an expanded CAG repeat in exon 1 of the HD gene exhibit a progressive neurological phenotype similar to the motor symptoms of Huntington's disease. We have therefore evaluated the effects of the transgenic brain environment on the survival, differentiation, and function of intrastriatal striatal grafts and undertaken a preliminary analysis of the effects of the grafts on the development of neurological deficits in the host mice. Hemizygote transgenic and wild-type littermate female mice received striatal grafts at 10 weeks of age and were allowed to survive 6 weeks. Normal healthy grafts were seen to survive and differentiate within the striatum of transgenic mice in a manner comparable to that seen in control mice. The transgenic mice exhibited a progressive decline in body weight from 9 weeks of age and a progressive hypoactivity in an open field test of general locomotor behavior. Although striatal grafts exerted a statistically significant influence on several indices of this impairment, all behavioral effects were small and did not exert any clinically relevant effect on the profound neurological deficiency of the transgenic mice.
纹状体移植已被提议作为亨廷顿舞蹈病纹状体修复的一种潜在策略，但尚不清楚患病大脑是否会影响移植组织的存活。最近描述了一种转基因小鼠品系，其中HD基因外显子1中CAG重复序列扩增的半合子表现出与亨廷顿舞蹈病运动症状相似的进行性神经表型。因此，我们评估了转基因脑环境对纹状体内纹状体移植组织的存活、分化和功能的影响，并对移植组织对宿主小鼠神经功能缺损发展的影响进行了初步分析。半合子转基因和野生型同窝雌性小鼠在10周龄时接受纹状体移植，并存活6周。正常健康的移植组织在转基因小鼠的纹状体内存活并分化，其方式与对照小鼠相当。转基因小鼠从9周龄开始体重逐渐下降，在一般运动行为的旷场试验中活动逐渐减少。尽管纹状体移植对这种损伤的几个指标有统计学上的显著影响，但所有行为影响都很小，对转基因小鼠严重的神经功能缺损没有产生任何临床相关影响。
