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

Autor:	Tingaud-Sequeira A; Rare Diseases Genetics and Metabolism, INSERM U1211, SBM Department, University of Bordeaux, F-33076 Bordeaux, France., Mercier E; Rare Diseases Genetics and Metabolism, INSERM U1211, SBM Department, University of Bordeaux, F-33076 Bordeaux, France., Michaud V; Rare Diseases Genetics and Metabolism, INSERM U1211, SBM Department, University of Bordeaux, F-33076 Bordeaux, France.; Molecular Genetics Laboratory, Bordeaux University Hospital, F-33076 Bordeaux, France., Pinson B; SAM, TBMcore, CNRS UAR 3427, INSERM US005, Université Bordeaux, F-33076 Bordeaux, France., Gazova I; MRC Human Genetics Unit, University of Edinburgh, Edinburgh EH4 2XU, UK., Gontier E; Bordeaux Imaging Center, CNRS, INSERM, BIC, UMS 3420, US 4, University Bordeaux, F-33076 Bordeaux, France., Decoeur F; Bordeaux Imaging Center, CNRS, INSERM, BIC, UMS 3420, US 4, University Bordeaux, F-33076 Bordeaux, France., McKie L; MRC Human Genetics Unit, University of Edinburgh, Edinburgh EH4 2XU, UK., Jackson IJ; MRC Human Genetics Unit, University of Edinburgh, Edinburgh EH4 2XU, UK., Arveiler B; Rare Diseases Genetics and Metabolism, INSERM U1211, SBM Department, University of Bordeaux, F-33076 Bordeaux, France.; Molecular Genetics Laboratory, Bordeaux University Hospital, F-33076 Bordeaux, France., Javerzat S; Rare Diseases Genetics and Metabolism, INSERM U1211, SBM Department, University of Bordeaux, F-33076 Bordeaux, France.
Jazyk:	angličtina
Zdroj:	Genes [Genes (Basel)] 2022 Jun 27; Vol. 13 (7). Date of Electronic Publication: 2022 Jun 27.
DOI:	10.3390/genes13071164
Abstrakt:	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 Tyr c/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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu