The ocular albinism type 1 (OA1) gene controls melanosome maturation and size.
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.
Cortese
Katia
K
Telethon Institute of Genetics and Medicine (TIGEM), Naples, Italy.
Giordano
Francesca
F
Surace
Enrico M
EM
Venturi
Consuelo
C
Ballabio
Andrea
A
Tacchetti
Carlo
C
Marigo
Valeria
V
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
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