EQUINE MOTOR-NEURON DISEASE IS NOT LINKED TO CU ZN SUPEROXIDE-DISMUTASE MUTATIONS - SEQUENCE-ANALYSIS OF THE EQUINE CU/ZN SUPEROXIDE-DISMUTASE CDNA/

The cDNA encoding the equine copper/zinc superoxide dismutase (SOD1) w as cloned from leukocyte total RNA from healthy horses and its nucleot ide (nt) sequence was determined. We further sequenced the SOD1 gene f rom 16 horses diagnosed with equine motor neuron disease (EMND) and ei ght unrelated, clinically normal horses to determine if this disease, similar to amyotrophic lateral sclerosis (ALS) in humans, is linked to SOD1 mutations. The 465-bp SOD1 coding region in the horse encodes 15 3 amino acid (aa) residues. Equine SOD1 exhibited 81.8 and 79.9% seque nce identity to the human homolog at the nt and aa levels, respectivel y, with only five distinct aa in the two loops that constitute the act ive site of the enzyme. None of the human SOD1 mutations found in the familial form of ALS were detected in SOD1 of the 16 affected horses. Although DNA sequence analysis identified three potential polymorphism s in equine SOD1, these were silent and were found in both normal and EMND-afflicted horses. Al this time, there is no conclusive evidence f or EMND linkage to SOD1 mutations.