CLONING, EXPRESSION AND CHROMOSOMAL LOCALIZATION OF THE RAT PANCREATITIS-ASSOCIATED PROTEIN-III GENE

PAP III belongs to the family of pancreatitis-associated proteins, rec ently characterized as pancreatic secretory proteins structurally rela ted to C-type lectins, and whose expression is induced during the acut e phase of pancreatitis. In this paper, we describe the cloning, chara cterization and chromosomal localization of the rat PAP III gene. The gene was isolated from a genomic library using a PCR-based method and characterized over 2.5 kb of gene sequence and 1.7 kb of 5'-flanking s equence. The 5' end of the coding sequence was determined by primer ex tension of the PAP III transcript. The PAP III coding sequence spanned over six exons. We found striking similarities between PAP III and PA P I and II genes, in genomic organization as well as in promoter seque nces. Moreover, the rat PAP III gene was mapped to chromosome 4 using mouse-rat hybrid cells, a localization which coincides with that of th e PAP I and II genes. The three genes could therefore derive from the same ancestral gene by duplication. Expression of the PAP III gene was compared with that of PAPs I and II. Expression levels were similar i n pancreas, where PAP III mRNA concentration increased within 6 h foll owing induction of pancreatitis, reached maximal levels (> 200 times c ontrol values) at 24-48 h, and decreased thereafter. In the intestinal tract, where PAP II is not expressed, the pattern of PAP III expressi on was comparable with that of PAP I; fasting induced a decrease in it s mRNA concentration by more than 80%, which could be reversed within 6 h upon feeding. PAP III is therefore a new member of the PAP gene fa mily, more closely related to the PAP I gene.