title: Mitochondrial changes in motor neurons of homozygotes of leucine 126 TT deletion SOD1 transgenic mice.
abstract: We investigated the time course of ultrastructural changes of mitochondria in the spinal cord of homozygotes of Leu126TTdel SOD1 (superoxide dismutase 1) with FLAG (signal sequence at the C-terminal protein) transgenic mice (DF-homo). Non-Tg mice and wild-type human SOD1 with FLAG epitope transgenic mice (WF) were investigated as controls for non-onset Tg mice. Expansion and vacuolation of the mitochondrial matrix was exhibited in motor neurons in the anterior horns of DF-homo Tg mice at the presymptomatic stage. Such mitochondrial degeneration became severe at the postsymptomatic stage. In contrast, expansion of the mitochondrial inner-membrane space was not evident even at the terminal stage. Microvacuoles of cytoplasm and fibrillar inclusions were rarely shown from the early symptomatic stage. WF mice showed expansion and vacuolation of the mitochondrial inner membrane space at old age. Non-Tgs showed no obvious change in mitochondria. Gold-labeled human SOD1 immunoreactivity showed small amount of gold deposits in the vacuolated mitochondria. These results suggest that the expansion and vacuolation of mitochondrial matrix in the spinal cord of DF-homo transgenic mice is the first pathological change, but that it is not directly caused by the aggregation of an abnormal human SOD1 protein in intermembrane space of mitochondria.
authors.affiliation: Department of Neurology, Institute of Neurological Sciences, Tottori University, Yonago, Japan. kdoi@grape.med.tottori-u.ac.jp
authors.forename: Koji
authors.initials: K
authors.lastname: Doi
authors.forename: Toshiya
authors.initials: T
authors.lastname: Nakano
authors.forename: Michio
authors.initials: M
authors.lastname: Kitayama
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Kenichi
authors.initials: K
authors.lastname: Yasui
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Fukada
authors.forename: Shinichi
authors.initials: S
authors.lastname: Morino
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kaidoh
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakashima
authors.forename: Takao
authors.initials: T
authors.lastname: Inoué
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000473:pathology*; D000818:Animals; D004195:Disease Models, Animal; D006720:Homozygote; D006801:Humans; D007930:Leucine / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron; D008928:Mitochondria / Q000648:ultrastructure*; D009046:Motor Neurons / Q000648:ultrastructure*; D009842:Oligopeptides; D010455:Peptides / Q000235:genetics; D017384:Sequence Deletion; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1
chemical_list: D009842:Oligopeptides; D010455:Peptides; C000606290:SOD1 protein, human; C085706:FLAG peptide; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D007930:Leucine