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Published 1 August 2005. doi:10.1083/jcb.200501038
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 170, Number 3, 487-496
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Article

The epidermal barrier function is dependent on the serine protease CAP1/Prss8

Céline Leyvraz1, Roch-Philippe Charles1, Isabelle Rubera1, Marjorie Guitard1, Samuel Rotman2, Bernadette Breiden3, Konrad Sandhoff3, and Edith Hummler1

1 Département de Pharmacologie et de Toxicologie, Université de Lausanne, CH-1005 Lausanne, Switzerland
2 Institut de Pathologie, Université de Lausanne, CH-1005 Lausanne, Switzerland
3 Kekulé-Institut für Organische Chemie und Biochemie der Universität Bonn, D-53121 Bonn, Germany

Correspondence to Edith Hummler: Edith.Hummler{at}unil.ch

Serine proteases are proteolytic enzymes that are involved in the regulation of various physiological processes. We generated mice lacking the membrane-anchored channel-activating serine protease (CAP) 1 (also termed protease serine S1 family member 8 [Prss8] and prostasin) in skin, and these mice died within 60 h after birth. They presented a lower body weight and exhibited severe malformation of the stratum corneum (SC). This aberrant skin development was accompanied by an impaired skin barrier function, as evidenced by dehydration and skin permeability assay and transepidermal water loss measurements leading to rapid, fatal dehydration. Analysis of differentiation markers revealed no major alterations in CAP1/Prss8-deficient skin even though the epidermal deficiency of CAP1/Prss8 expression disturbs SC lipid composition, corneocyte morphogenesis, and the processing of profilaggrin. The examination of tight junction proteins revealed an absence of occludin, which did not prevent the diffusion of subcutaneously injected tracer (~600 D) toward the skin surface. This study shows that CAP1/Prss8 expression in the epidermis is crucial for the epidermal permeability barrier and is, thereby, indispensable for postnatal survival.

C. Leyvraz and R.-P. Charles contributed equally to this paper.

I. Rubera's present address is Laboratoire de Physiologie Cellulaire et Moléculaire, Université de Nice Sophia-Antipolis, 06108 Nice, Cedex 2, France.

M. Guitard's present address is Cutaneous Biology Research Center, Charlestown, MA 02129.

Abbreviations used in this article: CAP, channel-activating protease; ENaC, epithelial sodium channel; GPI, glycosyl-phosphatidylinositol; K, keratin; LSM, laser scanning microscopy; MT-SP1, membrane-type serine protease 1; Prss8, protease serine S1 family member 8; SC, stratum corneum; SG, stratum granulosum; TEWL, transepidermal water loss; TJ, tight junction.


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