RGD Reference Report - Rats expressing human cytosolic copper-zinc superoxide dismutase transgenes with amyotrophic lateral sclerosis: associated mutations develop motor neuron disease. - Rat Genome Database

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Rats expressing human cytosolic copper-zinc superoxide dismutase transgenes with amyotrophic lateral sclerosis: associated mutations develop motor neuron disease.

Authors: Nagai, M  Aoki, M  Miyoshi, I  Kato, M  Pasinelli, P  Kasai, N  Brown RH, JR  Itoyama, Y 
Citation: Nagai M, etal., J Neurosci. 2001 Dec 1;21(23):9246-54.
RGD ID: 2290184
Pubmed: PMID:11717358   (View Abstract at PubMed)
PMCID: PMC6763929   (View Article at PubMed Central)

Some cases of familial amyotrophic lateral sclerosis (ALS) are caused by mutations in the gene encoding cytosolic, copper-zinc superoxide dismutase (SOD1). We report here that rats that express a human SOD1 transgene with two different ALS-associated mutations (G93A and H46R) develop striking motor neuron degeneration and paralysis. As in the human disease and transgenic ALS mice, pathological analysis demonstrates selective loss of motor neurons in the spinal cords of these transgenic rats. In spinal cord tissues, this is accompanied by activation of apoptotic genes known to be activated by mutant SOD1 protein in vitro and in vivo. These animals provide additional support for the proposition that motor neuron death in SOD1-related ALS reflects one or more acquired, neurotoxic properties of the mutant SOD1 protein. The larger size of this rat model as compared with the ALS mice will facilitate studies involving manipulations of spinal fluid (implantation of intrathecal catheters for chronic therapeutic studies; CSF sampling) and spinal cord (e.g., direct administration of viral- and cell-mediated therapies).



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SD-Tg(SOD1*G93A)39Ratamyotrophic lateral sclerosis MODELIMP human transgene in rat modelRGD 
SD-Tg(SOD1*H46R)4Ratamyotrophic lateral sclerosis MODELIMP human transgene in rat modelRGD 
SOD1Humanmotor neuron disease  IMP human transgene in rat modelRGD 
Sod1Ratmotor neuron disease  ISOSOD1 (Homo sapiens)human transgene in rat modelRGD 
Sod1Mousemotor neuron disease  ISOSOD1 (Homo sapiens)human transgene in rat modelRGD 
SD-Tg(SOD1*G93A)39Ratparaplegia  IMP  RGD 
SD-Tg(SOD1*H46R)4Ratparaplegia  IMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Sod1  (superoxide dismutase 1)

Genes (Mus musculus)
Sod1  (superoxide dismutase 1, soluble)

Genes (Homo sapiens)
SOD1  (superoxide dismutase 1)


Additional Information