Linked Life Data

15857664

Source:http://linkedlifedata.com/resource/pubmed/id/15857664

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2005-4-28
pubmed:abstractText
Mutation of Cu/Zn superoxide dismutase (SOD1) contributes to a portion of the cases of familial amyotrophic lateral sclerosis (FALS). We previously reported on a FALS family whose members had a mutant form of SOD1 characterized by a 2-base pair (bp) deletion at codon 126 of the SOD1 gene. To investigate the cellular consequences of this mutation, we produced transgenic mice that expressed normal and mutated copies of human SOD1: wild-type SOD1 (W), wild-type SOD1 with a FLAG epitope at C-terminal (WF), mutated SOD1 with the 2-bp deletion (D), and SOD1 with the 2-bp deletion with FLAG (DF). The mice heterozygotic for the human mutated SOD1 (D and DF) showed distinct ALS-like motor symptoms, whereas the mice heterozygotic for the normal SOD1 (W and WF) mice did not. Homozygotes of D and DF lines showed the ALS symptoms at an earlier age and died earlier than the heterozygotes. By Northern blot analysis, the mRNAs for all human SOD1s were confirmed in these lines. All the human SOD1 proteins, except the D mutant, were detectable by immunoblot. The D protein was only confirmed when it was concentrated by immunoprecipitation. Neuropathologically, loss of spinal motor neurons and reactive gliosis were common features in the symptomatic lines. The remaining motor neurons in these mice also exhibited eosinophilic inclusions. The biochemical and pathological characteristics of these mice are quite similar to those of human FALS patients with same mutation. This intriguing model will provide an important source of information of the pathogenesis of FALS.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0169-328X
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
135
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
12-20
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15857664-Animals, pubmed-meshheading:15857664-Blotting, Northern, pubmed-meshheading:15857664-Blotting, Western, pubmed-meshheading:15857664-Disease Models, Animal, pubmed-meshheading:15857664-Gene Expression, pubmed-meshheading:15857664-Glial Fibrillary Acidic Protein, pubmed-meshheading:15857664-Gliosis, pubmed-meshheading:15857664-Heterozygote, pubmed-meshheading:15857664-Humans, pubmed-meshheading:15857664-Immunohistochemistry, pubmed-meshheading:15857664-Immunoprecipitation, pubmed-meshheading:15857664-Inclusion Bodies, pubmed-meshheading:15857664-Mice, pubmed-meshheading:15857664-Mice, Inbred C57BL, pubmed-meshheading:15857664-Mice, Transgenic, pubmed-meshheading:15857664-Motor Neuron Disease, pubmed-meshheading:15857664-Motor Neurons, pubmed-meshheading:15857664-Mutation, pubmed-meshheading:15857664-Peptides, pubmed-meshheading:15857664-RNA, Messenger, pubmed-meshheading:15857664-Spinal Cord, pubmed-meshheading:15857664-Superoxide Dismutase, pubmed-meshheading:15857664-Time Factors
pubmed:year
2005
pubmed:articleTitle
Mouse motor neuron disease caused by truncated SOD1 with or without C-terminal modification.
pubmed:affiliation
Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Nishi-cho 36-1,Yonago 683-8504, Japan. yawatana@grape.med.tottori-u.ac.jp
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't