title: The ocular albinism type 1 (OA1) gene controls melanosome maturation and size.
abstract: OBJECTIVE
  The authors took advantage of the Oa1 mutant mouse in combination with other albinism mouse models (i.e., Tyrosinase and membrane-associated transporter protein [Matp]) to study the function of Oa1, the gene mutated in ocular albinism type 1, in the RPE during development and after birth.
  
  
  METHODS
  Enzyme activity and protein localization were analyzed by immunohistochemistry of tyrosinase (Tyr) in Oa1-null mice. Ultrastructural analysis and morphometry were performed by electron microscopy, of the RPE in Oa1-knockout mouse and double-mutant mice of Oa1 with either Tyr or Matp.
  
  
  RESULTS
  Differently from other albinism models, Tyr activity was not impaired in Oa1-/- eyes. Hypopigmentation of the RPE in Oa1-/- mice is due to a reduced number of melanosomes. Analysis of Oa1-/-;Tyr(c-2J)/Tyr(c-2J) and Oa1-/-;Matp(uw)/Matp(uw) double-knockout mice, which display a block at stages II and III of melanosome maturation, respectively, revealed that Oa1 controls the rate of melanosome biogenesis at early stages of the organellogenesis, whereas the control on the organelle size is exerted at the final stage of melanosome development (stage IV).
  
  
  CONCLUSIONS
  The findings indicate that Oa1 is involved in the regulation of melanosome maturation at two steps. Acting at early maturation stages, Oa1 controls the abundance of melanosomes in RPE cells. At later stages, Oa1 has a function in the maintenance of a correct melanosomal size. This study helps to define ocular albinism type 1 as a defect in melanosome organellogenesis and not in melanin production.
authors.affiliation: Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Cortese
authors.forename: Francesca
authors.initials: F
authors.lastname: Giordano
authors.forename: Enrico M
authors.initials: EM
authors.lastname: Surace
authors.forename: Consuelo
authors.initials: C
authors.lastname: Venturi
authors.forename: Andrea
authors.initials: A
authors.lastname: Ballabio
authors.forename: Carlo
authors.initials: C
authors.lastname: Tacchetti
authors.forename: Valeria
authors.initials: V
authors.lastname: Marigo
mesh_terms: D016117:Albinism, Ocular / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D018929:Cell Culture Techniques; D005136:Eye Proteins / Q000502:physiology*; D019084:Fluorescent Antibody Technique, Indirect; D017496:Hypopigmentation / Q000378:metabolism; D020460:Melanosomes / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism; D038081:Organogenesis; D010857:Pigment Epithelium of Eye / Q000378:metabolism* / Q000648:ultrastructure; D043562:Receptors, G-Protein-Coupled; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027981:Symporters
chemical_list: D005136:Eye Proteins; C506821:Gpr143 protein, mouse; C486338:Matp protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D043562:Receptors, G-Protein-Coupled; D027981:Symporters; D014442:Monophenol Monooxygenase