Characterization of the gene encoding mouse mast cell protease 8 (mMCP-8),and a comparative analysis of hematopoietic: serine pretense genes

Serine proteases are important granule constituents in several of the major hematopoietic cell lineages. We present here the nucleotide sequence of th e gene encoding mouse mast cell protease 8 (mMCP-8). mMCP-8 was initially i solated as a cDNA from a mouse mast cell line, but has recently been found to be expressed primarily by mouse basophils. mMCP-8 and its rat homologues , rMCP-8, -9, and -10, form a new group of mast cell/basophil proteases, wh ich are more closely related to the T-cell granzymes and neutrophil catheps in G than to the mast cell tryptases and chymases. A dot matrix comparison of the mMCP-8 gene with other closely related hematopoietic serine protease genes shows detectable homology only in the exonic regions of the genes. N o indication for conservation in the promoter region or introns was observe d. This latter finding indicates that the upstream regulatory region has ev olved at a relatively high rate. However, despite the low degree of direct sequence conservation, no major differences in the sizes of introns or exon s were observed between mMCP-8 and genes for the closest related hematopoie tic serine proteases, the mouse T-cell granzymes and cathepsin G, indicatin g that after evolutionary separation from the T-cell granzymes and cathepsi n G, the majority of mutations primarily involved single base pair substitu tions or short insertions or deletions.