Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Proc Natl Acad Sci U S A ; 99(3): 1604-9, 2002 Feb 05.
Article in English | MEDLINE | ID: mdl-11818550

ABSTRACT

Transgenic overexpression of Cu(+2)/Zn(+2) superoxide dismutase 1 (SOD1) harboring an amyotrophic lateral sclerosis (ALS)-linked familial genetic mutation (SOD1(G93A)) in a Sprague-Dawley rat results in ALS-like motor neuron disease. Motor neuron disease in these rats depended on high levels of mutant SOD1 expression, increasing from 8-fold over endogenous SOD1 in the spinal cord of young presymptomatic rats to 16-fold in end-stage animals. Disease onset in these rats was early, approximately 115 days, and disease progression was very rapid thereafter with affected rats reaching end stage on average within 11 days. Pathological abnormalities included vacuoles initially in the lumbar spinal cord and subsequently in more cervical areas, along with inclusion bodies that stained for SOD1, Hsp70, neurofilaments, and ubiquitin. Vacuolization and gliosis were evident before clinical onset of disease and before motor neuron death in the spinal cord and brainstem. Focal loss of the EAAT2 glutamate transporter in the ventral horn of the spinal cord coincided with gliosis, but appeared before motor neuron/axon degeneration. At end-stage disease, gliosis increased and EAAT2 loss in the ventral horn exceeded 90%, suggesting a role for this protein in the events leading to cell death in ALS. These transgenic rats provide a valuable resource to pursue experimentation and therapeutic development, currently difficult or impossible to perform with existing ALS transgenic mice.


Subject(s)
Excitatory Amino Acid Transporter 2/physiology , Motor Neuron Disease/genetics , Superoxide Dismutase/genetics , Amino Acid Substitution , Animals , Animals, Genetically Modified , Brain/metabolism , Brain/pathology , Disease Models, Animal , Excitatory Amino Acid Transporter 2/blood , Excitatory Amino Acid Transporter 2/deficiency , Excitatory Amino Acid Transporter 2/genetics , Humans , Immunohistochemistry , Motor Neuron Disease/enzymology , Motor Neuron Disease/metabolism , Motor Neuron Disease/pathology , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Mutagenesis, Site-Directed , Rats , Rats, Sprague-Dawley , Spinal Cord/metabolism , Spinal Cord/pathology , Superoxide Dismutase/blood , Superoxide Dismutase-1 , Time Factors
SELECTION OF CITATIONS
SEARCH DETAIL
...