The SOD1 gene encodes the superoxide dismutase 1 (SOD1) protein, which is a ubiquitous enzyme that catalyzes the dismutation of superoxide, a reactive oxygen species (ROS), into hydrogen peroxide and oxygen. Superoxide is a harmful molecule that can damage cells if not neutralized. SOD1 plays an important role in protecting cells from oxidative stress, which is damage caused by ROS. SOD1 is expressed in all cells in the body, but it is especially abundant in tissues that are particularly vulnerable to oxidative stress, such as the brain and nervous system. SOD1 expression is regulated by several factors, including oxidative stress itself. When cells are exposed to oxidative stress, SOD1 expression is increased to help protect cells from damage. Mutations in the SOD1 gene can cause several diseases, including amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease ^[1-2]. ALS is characterized by the progressive loss of motor neurons, which are the cells that control muscle movement. The SOD1 G94A mutation is one of the most common SOD1 mutations associated with ALS. The mutation results in a change in the amino acid sequence of the SOD1 protein at position 94, from glycine to alanine. This change in amino acid sequence destabilizes the SOD1 protein and makes it more prone to aggregation ^[3]. SOD1 aggregates are toxic to cells and can lead to cell death. The SOD1 G93A and G94A mutations refer to the same variant expressed under different amino acid numbering standards: G94A (modern/database standard) includes the initiating methionine, while G93A (traditional/model convention) reflects the mature protein after its removal.

The RCL-huSOD1-G94A mouse is a genetically engineered mouse model for conditional expression of the mutant human SOD1 gene, generated by knocking the sequence CAG promoter-loxP-PGK-Neo-6xSV40 pA-loxP-Mutant Human SOD1 Genomic DNA (ATG start codon to TAA stop codon)-WPRE-BGH pA into intron 1 of the ROSA26. When crossed with Cre recombinase‑expressing driver mice, sequence recombination occurs in Cre‑positive cells and tissues of the progeny. Cre‑mediated excision of the LSL expression‑stop cassette enables specific expression of the human SOD1 G94A mutant. This model can be used to investigate the mechanisms and therapeutic strategies of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS).