RESTORATION OF BRAIN-STEM AUDITORY-EVOKED POTENTIALS BY GENE-TRANSFER IN SHIVERER MICE
RESTORATION OF BRAIN-STEM AUDITORY-EVOKED POTENTIALS BY GENE-TRANSFER IN SHIVERER MICE
复制标题
DOI：
10.1177/000348949410300606
复制
发表时间：
1994-06-01
影响因子：
1.4
通讯作者：
YOO, TJ
中科院分区：
文献类型：
--
作者：
FUJIYOSHI, T;HOOD, L;YOO, TJ
我们研究了颤抖小鼠作为模型，用于纠正由中枢神经系统（CNS）遗传异常引起的听力障碍。Shiverer小鼠是髓鞘碱性蛋白（MBP）基因中常染色体隐性突变（缺失）的纯合子，MBP是CNS髓鞘的主要蛋白质组分。在耳蜗神经的电子显微镜观察下，颤抖小鼠的CNS部分显示髓鞘化不足，但外周部分，包括螺旋神经节细胞，是正常的。我们通过显微注射MBP粘粒克隆到颤抖小鼠受精卵的原核中来产生MBP转基因小鼠。发现转基因小鼠的MBP水平恢复到正常水平的25%。转基因小鼠中有更多轴突比颤抖小鼠中有髓鞘，但髓鞘没有正常对照组那么厚。脑干诱发电位各峰间潜伏期在颤抖小鼠中延长，在转基因小鼠中改善。本研究为中枢神经系统异常引起的听力障碍的基因治疗提供了一个范例。我们讨论了研究动物和人类遗传性听力障碍或耳聋的一些策略。
We studied the shiverer mouse as a model for correcting hearing disorders resulting from genetic abnormalities of the central nervous system (CNS). Shiverer mice are homozygous for an autosomal recessive mutation (deletion) in the gene for myelin basic protein (MBP), a major protein component of the myelin sheath in the CNS. Under electron microscopic observation of the cochlear nerve, the CNS portion in shiverer mice showed hypomyelination, but the peripheral portion, including spiral ganglion cells, was normal. We produced MBP-transgenic mice by microinjection of an MBP cosmid clone into the pronucleus of fertilized eggs from shiverer mice. The transgenic mice were found to recover MBP levels up to 25% of normal. A greater number of axons in the transgenic mice were myelinated than in the shiverer mice, but the myelin sheath was not as thick as in normal controls. Every interpeak latency of brain stem auditory-evoked potentials was prolonged in the shiverer mice and improved in the transgenic mice. This study provides an example of gene therapy for hearing disorders caused by a CNS abnormality. We discuss some strategies for researching genetic hearing impairment or deafness in both animals and humans.