title: Deletion of the gene encoding proprotein convertase 5/6 causes early embryonic lethality in the mouse.
abstract: 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(Delta4)-deficient allele missing exon 4 that encodes the catalytic Asp173. While Delta4/+ heterozygotes were healthy and fertile, genotyping of progeny obtained from Delta4/+ interbreeding indicated that Delta4/Delta4 embryos died between embryonic days 4.5 and 7.5. These data demonstrate that Pcsk5 is an essential gene.
authors.affiliation: Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec H2W 1R7, Canada.
authors.forename: Rachid
authors.initials: R
authors.lastname: Essalmani
authors.forename: Josée
authors.initials: J
authors.lastname: Hamelin
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Marcinkiewicz
authors.forename: Ann
authors.initials: A
authors.lastname: Chamberland
authors.forename: Majambu
authors.initials: M
authors.lastname: Mbikay
authors.forename: Michel
authors.initials: M
authors.lastname: Chrétien
authors.forename: Nabil G
authors.initials: NG
authors.lastname: Seidah
authors.forename: Annik
authors.initials: A
authors.lastname: Prat
mesh_terms: D000302:Adrenal Cortex / Q000201:enzymology; D000818:Animals; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000201:enzymology*; D047108:Embryonic Development / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005804:Genes, Lethal; D006801:Humans; D007422:Intestines / Q000201:enzymology; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D045702:Proprotein Convertase 5 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D007527:Isoenzymes; D012333:RNA, Messenger; D045702:Proprotein Convertase 5