title: Essential role of Elovl4 in very long chain fatty acid synthesis, skin permeability barrier function, and neonatal survival.
abstract: Mutations in the gene ELOVL4 have been shown to cause stargardt-like macular dystrophy. ELOVL4 is part of a family of fatty acid elongases and is yet to have a specific elongase activity assigned to it. We generated Elovl4 Y270X mutant mice and characterized the homozygous mutant as well as homozygous Elovl4 knockout mice in order to better understand the function or role of Elovl4. We found that mice lacking a functional Elovl4 protein died perinatally. The cause of death appears to be from dehydration due to faulty permeability barrier formation in the skin. Further biochemical analysis revealed a significant reduction in free fatty acids longer than C26 in homozygous mutant and knockout mouse skin. These results implicate the importance of these long chain fatty acids in skin barrier development. Furthermore, we suggest that Elovl4 is likely involved in the elongation of C26 and longer fatty acids.
authors.affiliation: Department of Ophthalmology and Visual Sciences, Moran Eye Center, University of Utah School of Medicine, Salt Lake City, UT 84132, USA.
authors.forename: D Joshua
authors.initials: DJ
authors.lastname: Cameron
authors.forename: Zongzhong
authors.initials: Z
authors.lastname: Tong
authors.forename: Zhenglin
authors.initials: Z
authors.lastname: Yang
authors.forename: Jack
authors.initials: J
authors.lastname: Kaminoh
authors.forename: Shin
authors.initials: S
authors.lastname: Kamiyah
authors.forename: Haoyu
authors.initials: H
authors.lastname: Chen
authors.forename: Jiexi
authors.initials: J
authors.lastname: Zeng
authors.forename: Yali
authors.initials: Y
authors.lastname: Chen
authors.forename: Ling
authors.initials: L
authors.lastname: Luo
authors.forename: Kang
authors.initials: K
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D003681:Dehydration; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000096:biosynthesis* / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D016014:Linear Models; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D010539:Permeability; D012867:Skin / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D012879:Skin Physiological Phenomena; D015996:Survival Rate
chemical_list: C498834:Elovl4 protein, mouse; D005136:Eye Proteins; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D008565:Membrane Proteins