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标题：Reduction of axonal caliber does not alleviate motor neuron disease caused by mutant superoxide dismutase 1
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作者：Minh Dang Nguyen ; Roxanne C. Larivière ; Jean-Pierre Julien 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2000
卷号：97
期号：22
页码：12306-12311
DOI：10.1073/pnas.97.22.12306
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：It is well established that motor neurons with large axon caliber are selectively affected in amyotrophic lateral sclerosis (ALS). To investigate whether high neurofilament (NF) content and large axonal caliber are factors that predispose motor neurons to selective degeneration in ALS, we generated mice expressing a mutant form of superoxide dismutase 1 (SOD1G37R) linked to familial ALS in a context of one allele for each NF gene being disrupted. A {approx}40% decrease of NF protein content detected in triple heterozygous knockout mice shifted the calibers of large axons in L5 ventral root from 5-9 {micro}m to 1-5 {micro}m, altering neither the normal subunit stoichiometry and morphological distribution of NFs nor levels of other cytoskeletal proteins. This considerable reduction in NF burden and caliber of axons did not extend the life span of SOD1G37R mice nor did it alleviate the loss of motor axons. Moreover, increasing the density of NFs in axons by overexpressing a NF-L transgene did not accelerate disease in SOD1G37R mice. These results do not support the current view that high NF content and large caliber of axons may account for the selective vulnerability of motor neurons in ALS caused by mutant SOD1.
关键词：amyotrophic lateral sclerosis ; Cu/Zn superoxide dismutase ; neurofilaments ; transgenic mice ; knockout mice