Mice hemizygous for this G85R-SOD1 transgene are viable and fertile, with transgenic expression of a G85R mutant form of human SOD1 associated with human familial Amyotrophic Lateral Sclerosis (ALS). Mice from this founder line (line 148) exhibit unaltered endogenous SOD1 activity; the G85R mutation is characterized as an "enzymatically inactive" mutation. Like wildtype SOD1, the G85R mutant SOD1 protein also forms monomer-misfolded oligomers associated with degenerating motor neurons.
Hemizygotes develop symptoms and pathology resembling human ALS; becoming paralyzed in one or more limbs due to loss of motor neurons from the spinal cord. On the C57BL/6 genetic background, hemizygous mice have a longer lifespan (median lifespan of 361 days). After the first initial phenotype observation, the disease progresses rapidly with death around 12-13 months of age. The onset and progression of motor dysfunction is accompanied by weight loss. For more detailed information, please view graph of B6.Cg-Tg(SOD1*G85R)148Dwc/J survival and weight data 2009-2010. [pdf]
These G85R-SOD1 transgenic mice may be useful in studying neuromuscular disorders, including Amyotrophic Lateral Sclerosis (ALS or Lou Gehrig's Disease).
In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. As the G85R-SOD1 transgenic mice were originally created on a mixed genetic background, it should be noted that the phenotype of these transgenic mice on a C57BL/6-congenic background may vary greatly from that originally described. We will modify the strain description if necessary as published results become available.
