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Molecular and Cellular Biology, January 2006, p. 354-361, Vol. 26, No. 1
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.1.354-361.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Deletion of the Gene Encoding Proprotein Convertase 5/6 Causes Early Embryonic Lethality in the Mouse

Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec H2W 1R7, Canada,¹ Diseases of Aging Program, Ottawa Health Research Institute, 725 Parkdale Avenue, Ottawa, Ontario K1Y 4K9, Canada²

Received 7 September 2005/ Returned for modification 7 October 2005/ Accepted 14 October 2005

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 Pcsk5⁴-deficient allele missing exon 4 that encodes the catalytic Asp₁₇₃. While 4/+ heterozygotes were healthy and fertile, genotyping of progeny obtained from 4/+ interbreeding indicated that 4/4 embryos died between embryonic days 4.5 and 7.5. These data demonstrate that Pcsk5 is an essential gene.

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