Characterization and localization of the genes for mouse proteinase-3 (Prtn3) and neutrophil elastase (Ela2)

Proteinase-3 (PR-3) and neutrophil elastase (NE) are polymorphonuclear leuk ocyte serine proteinases that de grade extracellular matrix proteins includ ing elastin and appear to be involved in the pathogenesis of several diseas es characterized by tissue destruction most notably emphysema and Wegener's granulomatosis. In this report we characterize and compare the mouse PR-3 and NE genes and establish by FISH analysis a common location on mouse chro mosome 10C2. Each gene consists of five exons and four introns conserving t he typical granule-associated serine proteinase gene structure. The mouse P R-3 gene (Prtn3) is approximately 3.7 kb and is within 2.2 kb of the smalle r (1.7 kb) NE gene (Ela2). The larger size of Prtn3 is accounted forby diff erences in intron sizes. A comparison between the mouse and human PR-3 cDNA reveals 73% homology, however, this drops to 60% when the amino acid seque nces are compared. Homology between the mouse and human NE cDNA is 77% for both the cDNA and amino acid sequences. The catalytic triad and its placeme nt are conserved among the four genes. The proximal promoter of mouse Prtn3 contains a TATA box, c-myb and an ets transcriptional site. As these are f unctional elements in the mouse Ela2 promoter they may also be important in the expression of Prtn3.