The Dct-/- Mouse Model to Unravel Retinogenesis Misregulation in Patients with Albinism

We have recently identified DCT encoding dopachrome tautomerase (DCT) as the eighth gene for oculocutaneous albinism (OCA). Patients with loss of function of DCT suffer from eye hypopigmentation and retinal dystrophy. Here we investigate the eye phenotype in Dct mice. We show that their retinal pigmented epithelium (RPE) is severely hypopigmented from early stages, contrasting with the darker melanocytic tissues. Multimodal imaging reveals specific RPE cellular defects. Melanosomes are fewer with correct subcellular localization but disrupted melanization. RPE cell size is globally increased and heterogeneous. P-cadherin labeling of Dct(-/-) newborn RPE reveals a defect in adherens junctions similar to what has been described in tyrosinase-deficient Tyrc/c embryos. The first intermediate of melanin biosynthesis, dihydroxyphenylalanine (L-Dopa), which is thought to control retinogenesis, is detected in substantial yet significantly reduced amounts in Dct(-/-) postnatal mouse eyecups. L-Dopa synthesis in the RPE alone remains to be evaluated during the critical period of retinogenesis. The Dct / mouse should prove useful in understanding the molecular regulation of retinal development and aging of the hypopigmented eye. This may guide therapeutic strategies to prevent vision deficits in patients with albinism.

Automated summary

We have identified DCT encoding dopachrome tautomerase (DCT) as the eighth gene for oculocutaneous albinism. Loss of DCT function leads to eye hypopigmentation and retinal dystrophy. By investigating Dct mice, we found severe hypopigmentation in their retinal pigmented epithelium (RPE) from early stages, with specific cellular defects. Understanding the molecular regulation of retinal development and aging of the hypopigmented eye may help guide therapeutic strategies for patients with albinism.