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 p...

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Bibliographic Details
Published in:Genes 2022-07, Vol.13 (7), p.1164
Main Authors: Tingaud-Sequeira, Angèle, Mercier, Elina, Michaud, Vincent, Pinson, Benoît, Gazova, Ivet, Gontier, Etienne, Decoeur, Fanny, McKie, Lisa, Jackson, Ian J., Arveiler, Benoît, Javerzat, Sophie
Format: Article
Language:English
Subjects:
Adherens junctions
Aging
Albinism
Cadherins
Cell size
Critical period
Dihydroxyphenylalanine
Dopachrome isomerase
Embryos
Enzymes
Epithelium
Eye
Genetics
Genotype & phenotype
Glycerol
Hair
Human health and pathology
Iris
Levodopa
Life Sciences
Localization
Melanin
Melanization
Melanosomes
Morphology
Phenotypes
Photoreceptors
Pigmentation
Retina
Retinal degeneration
Retinal pigment epithelium
Retinogenesis
Sensory Organs
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Summary: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.
ISSN:2073-4425
2073-4425
DOI:10.3390/genes13071164