Amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) is a progressive neurodegenerative disease primarily affecting motor neurons in the spinal cord, brainstem and motor cortex. While most cases of ALS are sporadic, ~10% are familial (FALS) with ~20% of FALS caused by a mutation in the SOD1 gene. Disease manifestation and severity are viable in sporadic ALS as well as FALS. 
 The SOD1-G93A (or G93A-SOD1) transgene has a human SOD1 gene with the G93A mutation associated with FALS - including its' endogenous human promoter/enhancer sequences. Hemizygous mice from the original SOD1-G93A founder line contained ~25 transgene copies at a single locus on distal chromosome 12 - resulting in motor neuron pathology and progressive weakness similar to ALS patients, and ultimately leading to death: 50% survival at ~130 days (mixed B6;SJL background; see Stock No. <a href="https://www.jax.org/strain/002726">002726</a>). From that original line, the "very low expressing" subline (VLE G93A SOD1 Tg) was identified having retained ~4 transgene copies as hemizygotes (Stock No. 032166) - resulting in a variable penetrance of clinical ALS phenotype, prolonged survival and protracted pathologic loss of motor neurons [<a href="https://www.ncbi.nlm.nih.gov/pubmed/24945277">Deitch et al. 2014 PLoS One 9:e99879</a>]. 
 Specifically, the phenotype of hemizygous VLE G93A SOD1 Tg mice (~4 transgene copies) on a (C57BL/6J x SJL/J)F1 genetic background is described below. While weakness can start at 9 months, only ~74% of mice 18 months or older demonstrate disease. VLE G93A SOD1 Tg mice show decreased motor neurons compared to non-transgenic mice, as well as increased cytoplasmic translocation of TDP-43. Whereas hemizygotes from the original SOD1-G93A Tg line (~25 transgene copies) have nearly 100% penetrance of motor weakness leading to death, these VLE G93A SOD1 Tg mice have incomplete penetrance of both clinical disease and shortened life span. In fact, ~20% of mice older than 24 months show no motor symptoms, and only ~18% of VLE G93A SOD1 Tg mice older than 22 months reach end stage. Because the variable phenotype penetrance and slow disease progression is similar to that of human ALS, these VLE G93A SOD1 Tg mice allow the study of pathologic events over time, as well as genetic and environmental modifiers that may not be causative, but can exacerbate or accelerate motor neuron disease. Of note, the phenotype of homozygous VLE G93A SOD1 Tg mice (~8 transgene copies) is expected to be more severe, but homozygotes have not not been full characterized to date (September 2018).
 The donating investigator reports their observed coat colors were agouti, tan/yellow with pink eyes, black or white (albino).

Use of MICE by companies or for-profit entities requires a license.

VLE G93A SOD1 Tg mice are a very low expressing subline of SOD1-G93A on a B6SJL genetic background. VLE G93A SOD1 Tg allow the study of genetic and environmental modifiers that may not be causative, but can exacerbate or accelerate motor neuron disease in familial amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease).
 In contrast to the higher-transgene copy SOD1-G93A line (Stock No. <a href="https://www.jax.org/strain/002726">002726</a>; ~25 transgene copies as hemizygotes) from which it was derived, these VLE G93A SOD1 Tg mice have ~4 transgene copies as hemizygotes - resulting in a variable penetrance of clinical ALS phenotype, prolonged survival and protracted pathologic loss of motor neurons. Approximately 20% do not manifest any symptoms of motor neuron disease.

Typically mice are recovered in 12-16 weeks. Contact Customer Service to place an order or for more information.

<a target="_blank" href="https://www.jax.org/jax-mice-and-services/customer-support" rel="noreferrer">Contact Customer Service</a> for more information.