De Rijk E P, Van Rijk A F, Van Esch E, De Jong W W, Wesseling P, Bloemendal H
NV.Organon, Department of Toxicology and Drug Disposition,The Netherlands.
Int J Exp Pathol. 2000 Aug;81(4):271-82. doi: 10.1046/j.1365-2613.2000.00161.x.
Homozygous mice transgenic for alphaA-crystallin, one of the structural eye lens proteins, developed hindlimb paralysis after 8 weeks of age. To unravel the pathogenesis of this unexpected finding and the possible role of alphaA-crystallin in this pathological process, mice were subjected to a histopathological and immunohistochemical investigation. Immunohistochemistry showed large deposits of alphaA-crystallin in the astrocytes of the spinal cord, and in the Schwann cells of dorsal roots and sciatic nerves. Additionally, microscopy showed dystrophic axons in the spinal cord and digestion chambers as a sign of ongoing demyelination in dorsal roots and sciatic nerves. Apart from a few areas with slight alphaA-crystallin-immunopositive structures, the brain was normal. Because the alphaA-crystallin protein expression appeared in specific cells of the nervous system (astrocytes and Schwann cells), the most plausible explanation for the paralysis is a disturbance of cell function caused by the excessive intracytoplasmic accumulation of the alphaA-crystallin protein. This is followed by a sequence of secondary changes (demyelination, axonal dystrophy) and finally arthrosis. In conclusion, alphaA-crystallin transgenic mice develop a peripheral and central neuropathy primarily affecting spinal cord areas at the dorsal side, dorsal root and sciatic nerve.
αA-晶状体蛋白（一种眼晶状体结构蛋白）的纯合转基因小鼠在8周龄后出现后肢麻痹。为了阐明这一意外发现的发病机制以及αA-晶状体蛋白在这一病理过程中的可能作用，对小鼠进行了组织病理学和免疫组织化学研究。免疫组织化学显示，αA-晶状体蛋白大量沉积于脊髓的星形胶质细胞以及背根和坐骨神经的施万细胞中。此外，显微镜检查显示脊髓中有营养不良性轴突，背根和坐骨神经中有消化腔，这是正在进行脱髓鞘的迹象。除了少数有轻微αA-晶状体蛋白免疫阳性结构的区域外，大脑正常。由于αA-晶状体蛋白的表达出现在神经系统的特定细胞（星形胶质细胞和施万细胞）中，麻痹最合理的解释是αA-晶状体蛋白在细胞质内过度积累导致细胞功能紊乱。随后会发生一系列继发性变化（脱髓鞘、轴突营养不良），最终导致关节病。总之，αA-晶状体蛋白转基因小鼠会发生主要影响脊髓背侧区域、背根和坐骨神经的周围和中枢神经病变。
