Journal
MOLECULAR AND CELLULAR BIOLOGY
Volume 26, Issue 1, Pages 354-361Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.26.1.354-361.2006
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PC5 belongs to the proprotein convertase family and activates precursor proteins by cleavage at basic sites during their transit through the secretory pathway and/or at the cell surface. These precursors include prohormones, proreceptors, growth factors, adhesion molecules, and viral glycoproteins. The Pcsk5 gene encodes two alternatively spliced isoforms, the soluble PC5A and transmembrane PC5B. We have carefully analyzed the expression of PC5 in the mouse during development and in adulthood by in situ hybridization, as well as in mouse tissues and various cell lines by quantitative reverse transcription-PCR. The data show that adrenal cortex and intestine are the richest sources of PC5A and PC5B, respectively. To better define the specific physiological roles of PC5, we have generated a mouse Pcsk5(Delta 4)-deficient allele missing exon 4 that encodes the catalytic Asp(173). While Delta 4/+ heterozygotes were healthy and fertile, genotyping of progeny obtained from Delta 4/+ interbreeding indicated that Delta 4/Delta 4 embryos died between embryonic days 4.5 and 7.5. These data demonstrate that Pcsk5 is an essential gene.
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