PARAOXONASE (PON1) GENE IN MICE - SEQUENCING, CHROMOSOMAL LOCALIZATION AND DEVELOPMENTAL EXPRESSION

Serum paraoxonase hydrolyses the toxic metabolites of several organoph osphorus insecticides, as well as the nerve agents soman and sarin. We have previously shown that elevated serum paraoxonase levels protect mice against organophosphate toxicity. In the present study, we determ ined the cDNA sequence and chromosomal location of the mouse paraoxona se gene, as well as its developmental expression in mice and rats. The mouse cDNA encodes a protein of 355 amino acids and shows 81% identit y with the human sequence. In situ hybridization demonstrated that the mouse paraoxonase gene maps to chromosome 6, a region conserved with the paraoxonase region of chromosome 7q21-22 in humans. Serum paraoxon ase activities toward three substrates, paraoxon, chlorpyrifos-oxon an d diazoxon, were very low at birth and increased with age reaching adu lt levels at 20 days in mice and 25 days in rats. The increase of seru m paraoxonase activity in developing animals correlates well with the increased resistance to organophosphate poisoning that has been report ed in previous studies.