Abstract
Complementation analysis of the urea cycle disorder ASAL deficiency has shown it to be characterized by striking genetic heterogeneity due to multiple alleles at a single locus, possibly the ASAL structural gene. We have examined the fibroblast ASAL monomer from 28 patients using denaturing polyacrylamide gel electrophoresis and protein blotting. Liver extracts and nine control fibroblast strains had a single protein band of MW 49,500 which cross-reacted with an anti-ASAL antisera. All 28 mutant strains had immunologically cross-reactive material (CRM) in the 49,500 region varying from trace to normal levels. Five mutants with the largest amount of 49,500 MW CRM also had the highest residual enzyme activity or the greatest ability to complement other mutants. In contrast to controls 27 of the 28 mutants had substantial lower MW CRM of 42,000, 38,000, 35,000, 34,000 and 30,500. In addition to the 49,500 MW band, several of these bands were also prominent in the blots of two obligate heterozygote strains. Only trace amounts of the lower MW bands were seen intermittently in controls. One mutant had unique bands of MW 39,000 and 25,000 suggesting the presence of a truncated polypeptide. These studies provide clear evidence of extensive heterogeneity in the abundance of the ASAL monomer (MW 49,500) in the mutant strains, and supporting evidence that ASAL deficiency affects the ASAL structural gene, resulting in the production of ASAL monomers with increased in vivo lability.
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Simard, L., O'Brien, W. & McInnes, R. MOLECULAR HETEROGENEITY OF THE ARGININOSUCCINASE (ASAL) MONOMER FROM ASAL-DEFICIENT FIBROBLASTS. Pediatr Res 18 (Suppl 4), 226 (1984). https://doi.org/10.1203/00006450-198404001-00797
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DOI: https://doi.org/10.1203/00006450-198404001-00797