Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

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, View ORCID ProfileIan J. Jackson, Benoît Arveiler, Sophie Javerzat
doi: https://doi.org/10.1101/2022.05.25.493436
Angèle Tingaud-Sequeira
1Rare Diseases Genetics and Metabolism, INSERM U1211, University of Bordeaux, Bordeaux, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elina Mercier
1Rare Diseases Genetics and Metabolism, INSERM U1211, University of Bordeaux, Bordeaux, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vincent Michaud
1Rare Diseases Genetics and Metabolism, INSERM U1211, University of Bordeaux, Bordeaux, France
2Molecular Genetics Laboratory, Bordeaux University Hospital, Bordeaux, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Benoît Pinson
3SAM, TBMcore - Université Bordeaux - CNRS UAR 3427 - INSERM US005, Bordeaux, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ivet Gazova
4MRC Human Genetics Unit, University of Edinburgh, Edinburgh, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Etienne Gontier
5Univ. Bordeaux, CNRS, INSERM, Bordeaux Imaging Center, BIC, UMS 3420, US 4, F-33000 Bordeaux, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fanny Decoeur
5Univ. Bordeaux, CNRS, INSERM, Bordeaux Imaging Center, BIC, UMS 3420, US 4, F-33000 Bordeaux, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lisa McKie
4MRC Human Genetics Unit, University of Edinburgh, Edinburgh, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ian J. Jackson
4MRC Human Genetics Unit, University of Edinburgh, Edinburgh, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ian J. Jackson
Benoît Arveiler
1Rare Diseases Genetics and Metabolism, INSERM U1211, University of Bordeaux, Bordeaux, France
2Molecular Genetics Laboratory, Bordeaux University Hospital, Bordeaux, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sophie Javerzat
1Rare Diseases Genetics and Metabolism, INSERM U1211, University of Bordeaux, Bordeaux, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: sophie.javerzat@u-bordeaux.fr
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

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 Statement

The authors have declared no competing interest.

Footnotes

  • sophie.javerzat{at}u-bordeaux.fr, benoit.arveiler{at}chu-bordeaux.fr, pinson{at}ibgc.cnrs.fr, ian.jackson{at}ed.ac.uk, etienne.gontier{at}u-bordeaux.fr

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted May 26, 2022.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
The Dct-/- mouse model to unravel retinogenesis misregulation in patients with albinism
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
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
bioRxiv 2022.05.25.493436; doi: https://doi.org/10.1101/2022.05.25.493436
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
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
bioRxiv 2022.05.25.493436; doi: https://doi.org/10.1101/2022.05.25.493436

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genetics
Subject Areas
All Articles
  • Animal Behavior and Cognition (3592)
  • Biochemistry (7562)
  • Bioengineering (5508)
  • Bioinformatics (20762)
  • Biophysics (10309)
  • Cancer Biology (7967)
  • Cell Biology (11625)
  • Clinical Trials (138)
  • Developmental Biology (6598)
  • Ecology (10190)
  • Epidemiology (2065)
  • Evolutionary Biology (13594)
  • Genetics (9532)
  • Genomics (12834)
  • Immunology (7917)
  • Microbiology (19525)
  • Molecular Biology (7651)
  • Neuroscience (42027)
  • Paleontology (307)
  • Pathology (1254)
  • Pharmacology and Toxicology (2196)
  • Physiology (3263)
  • Plant Biology (7029)
  • Scientific Communication and Education (1294)
  • Synthetic Biology (1949)
  • Systems Biology (5422)
  • Zoology (1114)