The ocular albinism type 1 (OA1) gene controls melanosome maturation and size

PURPOSE. The authors took advantage of the Oal mutant mouse in combination with other albinism mouse models (i.e., Tyrosinase and membrane-associated transporter protein [Matp]) to study the function of Oal, 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 Oal-null mice. Ultrastructural analysis and morphometry were performed by electron microscopy, of the RPE in Oal-knockout mouse and double-mutant mice of Oal 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 double-knockout mice, which display a block at stages II and III of melanosome maturation, respectively, revealed that Oal 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 Oal is involved in the regulation of melanosome maturation at two steps. Acting at early maturation stages, Oal controls the abundance of melanosomes in RPE cells. At later stages, Oal 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.