Rm. Luche et al., NOVEL MUTATIONS IN AN OTHERWISE STRICTLY CONSERVED DOMAIN OF CUZN SUPEROXIDE-DISMUTASE, Molecular and cellular biochemistry, 168(1-2), 1997, pp. 191-194
All mutations in the human gene for CuZn superoxide dismutase (CuZnSOD
) reported to date are associated with the disease amyotrophic lateral
sclerosis (ALS). These mutations, mostly of a familial nature (ALS 1,
MIM 105400), span all of the coding region of this enzyme except for
a highly conserved centrally located domain that includes all of exon
III. We describe the identification and characterization of two mutati
ons in this region, both found in mice. One mutation, a glutamate to l
ysine amino acid substitution was found in position 77 (E77K) of the s
train SOD1/Ei distributed by the Jackson Laboratory. The other mutatio
n, a lysine to glutamate substitution at position 70 (K70E) of a human
transgene, was discovered in mouse line TgHS/SF-155. Enzyme activity
measurements and heterodimer analysis of the CuZn SOD variant in SOD1/
Ei suggest a mild loss of activity, which differs from the enzyme acti
vity losses detected in patients with autosomal dominant ALS 1. Simila
rly, the presence of the mutant transgene in TgHS/SF 155 does not prod
uce any phenotypic manifestations.