title: Mice with targeted disruption of the fatty acid transport protein 4 (Fatp 4, Slc27a4) gene show features of lethal restrictive dermopathy.
abstract: 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.
authors.affiliation: Dept. of Internal Medicine IV, University of Heidelberg, Bergheimer Str. 58, 69115 Heidelberg, Germany. wolfgang_stremmel@med.uni-heidelberg.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Herrmann
authors.forename: Frank
authors.initials: F
authors.lastname: van der Hoeven
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Grone
authors.forename: Adrian Francis
authors.initials: AF
authors.lastname: Stewart
authors.forename: Lutz
authors.initials: L
authors.lastname: Langbein
authors.forename: Iris
authors.initials: I
authors.lastname: Kaiser
authors.forename: Gerhard
authors.initials: G
authors.lastname: Liebisch
authors.forename: Isabella
authors.initials: I
authors.lastname: Gosch
authors.forename: Florian
authors.initials: F
authors.lastname: Buchkremer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Drobnik
authors.forename: Gerd
authors.initials: G
authors.lastname: Schmitz
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stremmel
mesh_terms: D000818:Animals; D001835:Body Weight / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D002518:Ceramides / Q000096:biosynthesis; D004195:Disease Models, Animal; D004817:Epidermis / Q000002:abnormalities* / Q000378:metabolism* / Q000473:pathology; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D018390:Gene Targeting; D005804:Genes, Lethal / Q000235:genetics; D006257:Head / Q000002:abnormalities / Q000473:pathology; D007596:Joints / Q000002:abnormalities / Q000473:pathology; D050356:Lipid Metabolism; D008168:Lung / Q000002:abnormalities / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics; D026901:Membrane Transport Proteins; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D012868:Skin Abnormalities / Q000235:genetics / Q000378:metabolism*; D012873:Skin Diseases, Genetic / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D002518:Ceramides; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C493572:Slc27a4 protein, mouse