RT Journal Article SR Electronic T1 Rats Expressing Human Cytosolic Copper–Zinc Superoxide Dismutase Transgenes with Amyotrophic Lateral Sclerosis: Associated Mutations Develop Motor Neuron Disease JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 9246 OP 9254 DO 10.1523/JNEUROSCI.21-23-09246.2001 VO 21 IS 23 A1 Makiko Nagai A1 Masashi Aoki A1 Ichiro Miyoshi A1 Masaaki Kato A1 Piera Pasinelli A1 Noriyuki Kasai A1 Robert H. Brown, Jr A1 Yasuto Itoyama YR 2001 UL http://www.jneurosci.org/content/21/23/9246.abstract AB 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 andin 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).