The fatty acid transport protein family is a group of evolutionarily conserved proteins that are involved in the cellular uptake and metabolism of long and very long chain fatty acids. However, little is known about their respective physiological roles. To analyze the functional significance of fatty acid transport protein 4 (Fatp4, Slc27a4), we generated mice with a targeted disruption of the Fatp4 gene. Fatp4-null mice displayed features of a neonatally lethal restrictive dermopathy. Their skin was characterized by hyperproliferative hyperkeratosis with a disturbed epidermal barrier, a flat dermal–epidermal junction, a reduced number of pilo-sebaceous structures, and a compact dermis. The rigid skin consistency resulted in an altered body shape with facial dysmorphia, generalized joint flexion contractures, and impaired movement including suckling and breathing deficiencies. Lipid analysis demonstrated a disturbed fatty acid composition of epidermal ceramides, in particular a decrease in the C26:0 and C26:0-OH fatty acid substitutes. These findings reveal a previously unknown, essential function of Fatp4 in the formation of the epidermal barrier.
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23 June 2003
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June 23 2003
Mice with targeted disruption of the fatty acid transport protein 4 (Fatp 4, Slc27a4) gene show features of lethal restrictive dermopathy
Thomas Herrmann,
Thomas Herrmann
1Department of Internal Medicine IV, University of Heidelberg, 69115 Heidelberg, Germany
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Frank van der Hoeven,
Frank van der Hoeven
2Transgenic Core Facility, German Cancer Research Center, 69120 Heidelberg, Germany
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Hermann-Josef Gröne,
Hermann-Josef Gröne
3Department of Cellular and Molecular Pathology, German Cancer Research Center, 69120 Heidelberg, Germany
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Adrian Francis Stewart,
Adrian Francis Stewart
5Biotec, Technical University of Dresden, 01307 Dresden, Germany
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Lutz Langbein,
Lutz Langbein
4Department of Cell Biology, German Cancer Research Center, 69120 Heidelberg, Germany
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Iris Kaiser,
Iris Kaiser
1Department of Internal Medicine IV, University of Heidelberg, 69115 Heidelberg, Germany
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Gerhard Liebisch,
Gerhard Liebisch
6Institute of Clinical Chemistry, University of Regensburg, 93042 Regensburg, Germany
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Isabella Gosch,
Isabella Gosch
1Department of Internal Medicine IV, University of Heidelberg, 69115 Heidelberg, Germany
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Florian Buchkremer,
Florian Buchkremer
1Department of Internal Medicine IV, University of Heidelberg, 69115 Heidelberg, Germany
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Wolfgang Drobnik,
Wolfgang Drobnik
6Institute of Clinical Chemistry, University of Regensburg, 93042 Regensburg, Germany
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Gerd Schmitz,
Gerd Schmitz
6Institute of Clinical Chemistry, University of Regensburg, 93042 Regensburg, Germany
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Wolfgang Stremmel
Wolfgang Stremmel
1Department of Internal Medicine IV, University of Heidelberg, 69115 Heidelberg, Germany
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Thomas Herrmann
1Department of Internal Medicine IV, University of Heidelberg, 69115 Heidelberg, Germany
Frank van der Hoeven
2Transgenic Core Facility, German Cancer Research Center, 69120 Heidelberg, Germany
Hermann-Josef Gröne
3Department of Cellular and Molecular Pathology, German Cancer Research Center, 69120 Heidelberg, Germany
Adrian Francis Stewart
5Biotec, Technical University of Dresden, 01307 Dresden, Germany
Lutz Langbein
4Department of Cell Biology, German Cancer Research Center, 69120 Heidelberg, Germany
Iris Kaiser
1Department of Internal Medicine IV, University of Heidelberg, 69115 Heidelberg, Germany
Gerhard Liebisch
6Institute of Clinical Chemistry, University of Regensburg, 93042 Regensburg, Germany
Isabella Gosch
1Department of Internal Medicine IV, University of Heidelberg, 69115 Heidelberg, Germany
Florian Buchkremer
1Department of Internal Medicine IV, University of Heidelberg, 69115 Heidelberg, Germany
Wolfgang Drobnik
6Institute of Clinical Chemistry, University of Regensburg, 93042 Regensburg, Germany
Gerd Schmitz
6Institute of Clinical Chemistry, University of Regensburg, 93042 Regensburg, Germany
Wolfgang Stremmel
1Department of Internal Medicine IV, University of Heidelberg, 69115 Heidelberg, Germany
Address correspondence to Wolfgang Stremmel, Dept. of Internal Medicine IV, University of Heidelberg, Bergheimer Str. 58, 69115 Heidelberg, Germany. Tel.: 49-62-21-56-87-00. Fax: 49-62-21-56-41-16. E-mail: [email protected]
*
Abbreviations used in this paper: CER, ceramide; ESI-MS/MS, electrospray ionization tandem mass spectrometry; Fatp, fatty acid transport protein; FC, cholesterol; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PS, phosphatidylserine; SPM, sphingomyelin; TEWL, transepidermal water loss; X-gal, 5-bromo-4-chloro-3-indolyl-β-d-galactopyranoside.
Received:
July 15 2002
Revision Received:
May 01 2003
Accepted:
May 05 2003
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2003
J Cell Biol (2003) 161 (6): 1105–1115.
Article history
Received:
July 15 2002
Revision Received:
May 01 2003
Accepted:
May 05 2003
Citation
Thomas Herrmann, Frank van der Hoeven, Hermann-Josef Gröne, Adrian Francis Stewart, Lutz Langbein, Iris Kaiser, Gerhard Liebisch, Isabella Gosch, Florian Buchkremer, Wolfgang Drobnik, Gerd Schmitz, Wolfgang Stremmel; Mice with targeted disruption of the fatty acid transport protein 4 (Fatp 4, Slc27a4) gene show features of lethal restrictive dermopathy . J Cell Biol 23 June 2003; 161 (6): 1105–1115. doi: https://doi.org/10.1083/jcb.200207080
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