PT  - JOURNAL ARTICLE
AU  - Angèle Tingaud-Sequeira
AU  - Elina Mercier
AU  - Vincent Michaud
AU  - Benoît Pinson
AU  - Ivet Gazova
AU  - Etienne Gontier
AU  - Fanny Decoeur
AU  - Lisa McKie
AU  - Ian J. Jackson
AU  - Benoît Arveiler
AU  - Sophie Javerzat
TI  - The <em>Dct</em><sup>-/-</sup> mouse model to unravel retinogenesis misregulation in patients with albinism
AID  - 10.1101/2022.05.25.493436
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.05.25.493436
4099  - http://biorxiv.org/content/early/2022/05/25/2022.05.25.493436.short
4100  - http://biorxiv.org/content/early/2022/05/25/2022.05.25.493436.full
AB  - We have recently identified DCT encoding dopachrome tautomerase (DCT) as the 8th 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 melanisation. 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.Competing Interest StatementThe authors have declared no competing interest.