title: Fatty acid transport protein 1 can compensate for fatty acid transport protein 4 in the developing mouse epidermis.
abstract: Fatty acid transport protein (FATP) 4 is one of a family of six FATPs that facilitate long- and very-long-chain fatty acid uptake. Mice lacking FATP4 are born with tight, thick skin and a defective barrier; they die neonatally because of dehydration and restricted movements. Mutations in SLC27A4, the gene encoding FATP4, cause ichthyosis prematurity syndrome (IPS), characterized by premature birth, respiratory distress, and edematous skin with severe ichthyotic scaling. Symptoms of surviving patients become mild, although atopic manifestations are common. We previously showed that suprabasal keratinocyte expression of a Fatp4 transgene in Fatp4 mutant skin rescues the lethality and ameliorates the skin phenotype. Here we tested the hypothesis that FATP1, the closest FATP4 homolog, can compensate for the lack of FATP4 in our mouse model of IPS, as it might do postnatally in IPS patients. Transgenic expression of FATP1 in suprabasal keratinocytes rescued the phenotype of Fatp4 mutants, and FATP1 sorted to the same intracellular organelles as endogenous FATP4. Thus, FATP1 and FATP4 likely have overlapping substrate specificities, enzymatic activities, and biological functions. These results suggest that increasing expression of FATP1 in suprabasal keratinocytes could normalize the skin of IPS patients and perhaps prevent the atopic manifestations.
authors.affiliation: Renal Division, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Meei-Hua
authors.initials: MH
authors.lastname: Lin
authors.affiliation: Renal Division, Washington University School of Medicine, St. Louis, Missouri, USA; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri, USA. Electronic address: minerj@wustl.edu.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Miner
mesh_terms: D000818:Animals; D015783:Aniridia / Q000209:etiology / Q000235:genetics; D004817:Epidermis / Q000378:metabolism*; D050612:Fatty Acid Transport Proteins / Q000502:physiology*; D007057:Ichthyosis / Q000209:etiology / Q000235:genetics; D007235:Infant, Premature, Diseases / Q000209:etiology / Q000235:genetics; D007668:Kidney / Q000002:abnormalities; D051379:Mice; D011596:Psychomotor Disorders / Q000209:etiology / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000502:physiology
chemical_list: D050612:Fatty Acid Transport Proteins; D050796:STAT3 Transcription Factor; C493569:Slc27a1 protein, mouse; C493572:Slc27a4 protein, mouse; C494087:Stat3 protein, mouse