Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012 Feb 1;21(3):586-608.
doi: 10.1093/hmg/ddr494. Epub 2011 Oct 28.

Loss of ceramide synthase 3 causes lethal skin barrier disruption

Richard Jennemann  1 , Mariona Rabionet, Karin Gorgas, Sharon Epstein, Alexander Dalpke, Ulrike Rothermel, Aline Bayerle, Franciscus van der Hoeven, Silke Imgrund, Joachim Kirsch, Walter Nickel, Klaus Willecke, Howard Riezman, Hermann-Josef Gröne, Roger Sandhoff
Affiliations

Loss of ceramide synthase 3 causes lethal skin barrier disruption

Richard Jennemann et al. Hum Mol Genet. .

Abstract

The stratum corneum as the outermost epidermal layer protects against exsiccation and infection. Both the underlying cornified envelope (CE) and the intercellular lipid matrix contribute essentially to these two main protective barriers. Epidermis-unique ceramides with ultra-long-chain acyl moities (ULC-Cers) are key components of extracellular lipid lamellae (ELL) and are bound to CE proteins, thereby contributing to the cornified lipid envelope (CLE). Here, we identified human and mouse ceramide synthase 3 (CerS3), among CerS1-6, to be exclusively required for the ULC-Cer synthesis in vitro and of mouse CerS3 in vivo. Deficiency of CerS3 in mice results in complete loss of ULC-Cers (≥C26), lack of continuous ELL and a non-functional CLE. Consequently, newborn mutant mice die shortly after birth from transepidermal water loss. Mutant skin is prone to Candida albicans infection highlighting ULC-Cers to be pivotal for both barrier functions. Persistent periderm, hyperkeratosis and deficient cornification are hallmarks of mutant skin demonstrating loss of Cers to trigger a keratinocyte maturation arrest at an embryonic pre-barrier stage.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

  NODES
twitter 2