Equine motor neuron disease is not linked to Cu/Zn superoxide dismutase mutations: sequence analysis of the equine Cu/Zn superoxide dismutase cDNA.

This study disproves the hypothesis that equine motor neuron disease (EMND) in horses is linked to mutations of the Cu/Zn superoxide dismutase (SOD1) gene according to sequences analyzed from horses both with and without EMND.

Objective and Methodology

• The authors originally set out to explore if there was a potential linkage between EMND in horses and SOD1 gene mutations, mirroring the link seen between human ALS and SOD1 mutations.
• The equine SOD1 gene was first cloned and sequenced from healthy horses’ leukocyte total RNA to provide a reference sequence.
• Next, the SOD1 gene sequences of 16 horses diagnosed with EMND and 8 clinically normal horses were obtained and compared against the reference sequence.

Findings

• The 465-bp SOD1 coding region in the horse accounts for 153 amino acid residues. The equine SOD1 showed 81.8% and 79.9% sequence identity with human SOD1 at the nucleotide and amino acid levels, respectively.
• Distinct differences between human and equine SOD1 versions were observed, with five unique amino acids found in the active site of the equine SOD1 enzyme.
• Crucially, none of the SOD1 mutations associated with the familial form of ALS in humans were observed in any of the affected horses’ SOD1 genes.
• Three potential polymorphisms (variations in DNA sequence that can affect genes) were identified in equine SOD1. However, these were silent mutations, meaning they do not cause a notable change in the produced protein, and they were found in both healthy and EMND-affected horses.

Conclusion

• The study concluded that there is currently no solid evidence suggesting a link between SOD1 mutations and EMND in horses.
• Despite initial thoughts that the equine disease may share its genetic origin with a similar human disease (ALS), the findings indicate that this is not the case.