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

Angèle Tingaud-sequeira; Elina Mercier; Vincent Michaud; Benoît Pinson; Ivet Gazova; Etienne Gontier; Fanny Decoeur; Lisa Mckie; Ian J. Jackson; Benoît Arveiler; Sophie Javerzat

doi:10.3390/genes13071164

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

Angèle Tingaud-sequeira, Elina Mercier, Vincent Michaud, Benoît Pinson, Ivet Gazova, Etienne Gontier, Fanny Decoeur, Lisa Mckie, Ian J. Jackson, Benoît Arveiler, Sophie Javerzat

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

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

Original language	English
Article number	1164
Pages (from-to)	1164
Journal	Genes
Volume	13
Issue number	7
Early online date	27 Jun 2022
DOIs	https://doi.org/10.3390/genes13071164
Publication status	Published - 27 Jun 2022

Keywords / Materials (for Non-textual outputs)

Albinism, Oculocutaneous/genetics
Albinism/genetics
Animals
Disease Models, Animal
Humans
Intramolecular Oxidoreductases
Levodopa
Melanosomes
Mice
Monophenol Monooxygenase/genetics

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10.3390/genes13071164

The Dct−-− Mouse Model to Unravel Retinogenesis Misregulation in Patients with AlbinismFinal published version, 1.54 MB

https://www.mdpi.com/2073-4425/13/7/1164

MC_UU_00007/4 Mouse Models of Human Variation and Disease
Jackson, I.
1/04/18 → 31/03/23
Project: Research

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@article{5b7bb67fcacf4d618b5fd939bd608afe,

title = "The Dct−/− Mouse Model to Unravel Retinogenesis Misregulation in Patients with Albinism",

abstract = "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‐deficientTyrc/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",

keywords = "Albinism, Oculocutaneous/genetics, Albinism/genetics, Animals, Disease Models, Animal, Humans, Intramolecular Oxidoreductases, Levodopa, Melanosomes, Mice, Monophenol Monooxygenase/genetics",

author = "Ang{\`e}le Tingaud-sequeira and Elina Mercier and Vincent Michaud and Beno{\^i}t Pinson and Ivet Gazova and Etienne Gontier and Fanny Decoeur and Lisa Mckie and Jackson, {Ian J.} and Beno{\^i}t Arveiler and Sophie Javerzat",

note = "Funding Information: This research was funded by Genespoir, France, and l{\textquoteright}Agence Nationale de la Recherche, France, (grant number ANR-21-CE17-0041-01). I.G., L.M., and I.J.J. were funded by the MRC University Unit award to the MRC Human Genetics Unit, grant number MC_UU_00007/4. Electron Microscopy was performed on the Bordeaux Imaging Center, member of the FranceBioImaging national infrastructure (ANR-10-INBS-04). Funding Information: Funding: This research was funded by Genespoir, France, and l{\textquoteright}Agence Nationale de la Recherche, France, (grant number ANR‐21‐CE17‐0041‐01). I.G., L.M., and I.J.J. were funded by the MRC Uni‐ versity Unit award to the MRC Human Genetics Unit, grant number MC_UU_00007/4. Electron Microscopy was performed on the Bordeaux Imaging Center, member of the FranceBioImaging national infrastructure (ANR‐10‐INBS‐04). Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

month = jun,

day = "27",

doi = "10.3390/genes13071164",

language = "English",

volume = "13",

pages = "1164",

journal = "Genes",

issn = "2073-4425",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "7",

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TY - JOUR

T1 - The Dct−/− Mouse Model to Unravel Retinogenesis Misregulation in Patients with Albinism

AU - Tingaud-sequeira, Angèle

AU - Mercier, Elina

AU - Michaud, Vincent

AU - Pinson, Benoît

AU - Gazova, Ivet

AU - Gontier, Etienne

AU - Decoeur, Fanny

AU - Mckie, Lisa

AU - Jackson, Ian J.

AU - Arveiler, Benoît

AU - Javerzat, Sophie

N1 - Funding Information: This research was funded by Genespoir, France, and l’Agence Nationale de la Recherche, France, (grant number ANR-21-CE17-0041-01). I.G., L.M., and I.J.J. were funded by the MRC University Unit award to the MRC Human Genetics Unit, grant number MC_UU_00007/4. Electron Microscopy was performed on the Bordeaux Imaging Center, member of the FranceBioImaging national infrastructure (ANR-10-INBS-04). Funding Information: Funding: This research was funded by Genespoir, France, and l’Agence Nationale de la Recherche, France, (grant number ANR‐21‐CE17‐0041‐01). I.G., L.M., and I.J.J. were funded by the MRC Uni‐ versity Unit award to the MRC Human Genetics Unit, grant number MC_UU_00007/4. Electron Microscopy was performed on the Bordeaux Imaging Center, member of the FranceBioImaging national infrastructure (ANR‐10‐INBS‐04). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/6/27

Y1 - 2022/6/27

N2 - 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‐deficientTyrc/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

AB - 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‐deficientTyrc/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

KW - Albinism, Oculocutaneous/genetics

KW - Albinism/genetics

KW - Animals

KW - Disease Models, Animal

KW - Humans

KW - Intramolecular Oxidoreductases

KW - Levodopa

KW - Melanosomes

KW - Mice

KW - Monophenol Monooxygenase/genetics

U2 - 10.3390/genes13071164

DO - 10.3390/genes13071164

M3 - Article

C2 - 35885947

SN - 2073-4425

VL - 13

SP - 1164

JO - Genes

JF - Genes

IS - 7

M1 - 1164

ER -

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

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Keywords / Materials (for Non-textual outputs)

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MC_UU_00007/4 Mouse Models of Human Variation and Disease

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