Complete cDNA and 5' genomic sequences and multilevel regulation of the mouse catalase gene

Extensive studies over two decades have established strain- and tissue-specific temporal expression of the antioxidant enzyme catalase and have generated an acatalasemic strain of mice C3H/HeAnl/Cas-1b (Csb). This background permits the characterization of the molecular features of the regulation of this important housekeeping enzyme encoded by the gene Cas-1 localized to chromosome 2. We report the first complete cDNA sequence for Cas-1, including 659 bp of the 5' genomic upstream regulatory region. Cas-1 expression (e.g., mRNA, polypeptide, and enzyme activity) in tissues from appropriate strains is evaluated. The genotype- and strain-specific differences in tissue expression appear to be post-transcriptionally regulated. The mRNA stability is unaffected, and the regulation must involve translational efficiency or post-translational protein stability. The TATA-less 5' promoter is CG rich, with potential tissue-specific differences in methylation. The 3' UTR has unusual repeats [(CA)31, (T)15, (TGTGC)7] and may form mRNA-protein complexes. Here, 3' UTR binding protein(s) may account for transacting factors recognized in segregation studies. We propose that this housekeeping antioxidant enzyme is under multilevel regulation, and the determinants include both 5' and 3' Cas-1 sequences.