Gawlik Kinga I, Li Jia-Yi, Petersén Asa, Durbeej Madeleine
Muscle Biology Unit, Division for Cell and Matrix Biology, Department of Experimental Medical Science, University of Lund, Sweden.
Hum Mol Genet. 2006 Sep 15;15(18):2690-700. doi: 10.1093/hmg/ddl201. Epub 2006 Aug 7.
Absence of laminin alpha2 chain leads to a severe form of congenital muscular dystrophy (MDC1A) associated with peripheral neuropathy. Hence, future therapies should be aimed at alleviating both muscle and neurological dysfunctions. Pre-clinical studies in animal models have mainly focused on ameliorating the muscle phenotype. Here we show that transgenic expression of laminin alpha1 chain in muscles and the peripheral nervous system of laminin alpha2 chain deficient mice reduced muscular dystrophy and largely corrected the peripheral nerve defects. The presence of laminin alpha1 chain in the peripheral nervous system resulted in near-normal myelination, restored Schwann cell basement membranes and improved rotarod performance. In summary, we postulate that laminin alpha1 chain is an excellent substitute for laminin alpha2 chain in multiple tissues and suggest that treatment with laminin alpha1 chain may be beneficial for MDC1A in humans.
层粘连蛋白α2链的缺失会导致一种与周围神经病变相关的严重先天性肌营养不良症（MDC1A）。因此，未来的治疗应旨在缓解肌肉和神经功能障碍。动物模型的临床前研究主要集中在改善肌肉表型上。在此我们表明，在层粘连蛋白α2链缺陷小鼠的肌肉和周围神经系统中转基因表达层粘连蛋白α1链可减轻肌营养不良，并在很大程度上纠正周围神经缺陷。周围神经系统中层粘连蛋白α1链的存在导致髓鞘形成接近正常，恢复了施万细胞基底膜并改善了转棒试验表现。总之，我们推测层粘连蛋白α1链在多种组织中是层粘连蛋白α2链的极佳替代品，并表明用层粘连蛋白α1链治疗可能对人类MDC1A有益。
