title: A role for ELOVL4 in the mouse meibomian gland and sebocyte cell biology.
abstract: OBJECTIVE
  The meibum lipidome contains lipids with extremely long chain fatty acid (ELCFA) residues, longer than C28. Particular lipids based on extremely long chain (O-acyl)-ω-hydroxy fatty acids (OAHFA) are found in all mammal meibum and are proposed to stabilize the tear film by forming the interphase between its lipid and aqueous sublayers. The enzyme ELOVL4 is required for synthesis of ELCFA. We investigated whether Stgd3 mice, harboring mutations in ELOVL4 that have been shown to decrease the levels of its biosynthetic lipid products, would represent a model system in which to define the role of such lipids in meibum.
  
  
  METHODS
  Ocular phenotypes of wild-type mice were compared with those of Stgd3 mice. ELOVL4 expression in eyelid and back skin was characterized by immunohistochemical analysis. Anatomical changes within the eyelids of mutant mice were examined by hematoxylin and eosin staining of paraffin-embedded tissue.
  
  
  RESULTS
  Mutant mice had increased eyelid blink rates, a reluctance to maintain their eyes fully open, protruding meibomian gland (MG) orifices, and anatomical changes within the MG. In wild-type mice, ELOVL4 was strongly expressed within the holocrine meibomian and sebaceous glands. The enzyme localized to structures encircling lipid deposits within cells in both the early and late stages of differentiation. No ELOVL4 was detected within the central meibomian duct.
  
  
  CONCLUSIONS
  Stgd3 mice show changes that resemble clinical findings in patients with the evaporative type of dry eye disease, suggesting that further studies in this mouse model will provide a basis for better understanding of the causes of human dry eye.
authors.affiliation: Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, Texas, United States.
authors.forename: Anne
authors.initials: A
authors.lastname: McMahon
authors.forename: Hua
authors.initials: H
authors.lastname: Lu
authors.forename: Igor A
authors.initials: IA
authors.lastname: Butovich
mesh_terms: D000818:Animals; D001767:Blinking / Q000502:physiology; D004195:Disease Models, Animal; D015352:Dry Eye Syndromes / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D005143:Eyelids / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008537:Meibomian Glands / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D012627:Sebaceous Glands / Q000378:metabolism*; D012867:Skin / Q000378:metabolism
chemical_list: C498834:Elovl4 protein, mouse; D005136:Eye Proteins; D008565:Membrane Proteins
keywords: ELOVL4; lipids; meibocytes; sebocytes; tear film