Mice with targeted disruption of the fatty acid transport protein 4 (Fatp 4, Slc27a4) gene show features of lethal restrictive dermopathy.
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.
Herrmann
Thomas
T
Dept. of Internal Medicine IV, University of Heidelberg, Bergheimer Str. 58, 69115 Heidelberg, Germany. wolfgang_stremmel@med.uni-heidelberg.de
van der Hoeven
Frank
F
Grone
Hermann-Josef
HJ
Stewart
Adrian Francis
AF
Langbein
Lutz
L
Kaiser
Iris
I
Liebisch
Gerhard
G
Gosch
Isabella
I
Buchkremer
Florian
F
Drobnik
Wolfgang
W
Schmitz
Gerd
G
Stremmel
Wolfgang
W
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*
D002352:Carrier Proteins; D002518:Ceramides; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C493572:Slc27a4 protein, mouse