Characterization of superoxide dismutase (SOD-1 and SOD-2) activities in inbred mice: evidence for quantitative variability and possible nonallelic SOD-1 polymorphism.

Liver Cu/Zn (SOD-1) and Mn (SOD-2) superoxide dismutase activities were determined in 12 inbred mouse lines. SOD-2 activity varied from 5 to 8 U/mg protein but was never more than 5% of the total. SOD-1 activity varied from 112 (SJL/J) to 155 (RF/J) U/mg protein, with the 12 strains falling into three activity classes. No correlation between SOD-1 activity and H-2 histocompatibility phenotype was observed, i.e., these two loci do not appear linked as previously suggested [Novak, R., Bosze, Z., Matkovics, B. and Fachet, J. (1980). Science 207:86]. Several tissues in all strains exhibited three SOD-1 charge electromorphs which did not differ in relative proportions between strains or tissues. The pI values of these three isozymes were 4.0, 4.5, and 5.0, respectively. The pI value of SOD-2 was 7.7. Both SOD-1 and SOD-2 were sensitive to CHCl3/EtOH extraction, but this sensitivity was not electromorph specific. Quantitation of the SOD-1 isozymic pattern indicated that the electromorphs were present at a ratio of 1:6:23 in order of increasing pI. Fitting of these data to a binomial distribution showed that they were consistent with the presence of two SOD-1 subunits (chains) of unequal pI. The mole fractions of the two chains were calculated to be 0.14 (lower-pI chain) and 0.86 (higher-pI chain). Since the mice used were highly inbred, this pattern could be due to unequal rates of transcription of linked, nonallelic SOD-1 loci, although other explanations are possible. The activity differences between SJL/J and RF/J appear large enough and the data precise enough to make genetic studies on the control of SOD-1 expression in the mouse practicable.