Molecular cloning and characterization of the chromosomal for human lactoperoxidase

Lactoperoxidase (LPO) is an oxidoreductase secreted into milk, and plays an important role in protecting the lactating mammary gland and the intestinal tract of the newborn infants against pathogenic microorganisms. In this study, the human LPO chromosomal gene was molecularly cloned, and its gene organization was determined. The human LPO gene was found to be arranged with the myeloperoxidase (MPO) gene in a tail-to-tail manner. Similar to the human MPO and eosinophil peroxidase (EPO) genes, the human LPO gene is split by 11 introns and spans 28 kb. Unlike most introns in mammalian gene, the 5' splice donor sequence of intron 11 starts with GC instead of GT. When the minigene comprised of exon 11, intron 11 and exon 12 of the human LPO gene was introduced into COS cells, the correct splicing of the intron was found, suggesting the intron 11 of the human LPO gene is functional. The coding sequence of human LPO consists of 2136 bp, and codes for a protein of 712 amino acids. The amino acid sequence of human LPO has 51% similarity with those of both human MPO and EPO, suggesting that these peroxidase genes have evolved from a common ancestral gene. On the other hand, the nucleotide sequences of the 5' promoter regions of these peroxidase genes exhibit no similarity among them, which agrees with their tissue-specific expression.