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Morphological, behavioral and cellular analyses revealed different phenotypes in Wolfram syndrome wfs1a and wfs1b zebrafish mutant lines.
Crouzier, Lucie; Richard, Elodie M; Diez, Camille; Alzaeem, Hala; Denus, Morgane; Cubedo, Nicolas; Delaunay, Thomas; Glendenning, Emily; Baxendale, Sarah; Liévens, Jean-Charles; Whitfield, Tanya T; Maurice, Tangui; Delprat, Benjamin.
Affiliation
  • Crouzier L; MMDN, Université Montpellier, EPHE, INSERM, Montpellier, France.
  • Richard EM; MMDN, Université Montpellier, EPHE, INSERM, Montpellier, France.
  • Diez C; MMDN, Université Montpellier, EPHE, INSERM, Montpellier, France.
  • Alzaeem H; MMDN, Université Montpellier, EPHE, INSERM, Montpellier, France.
  • Denus M; MMDN, Université Montpellier, EPHE, INSERM, Montpellier, France.
  • Cubedo N; MMDN, Université Montpellier, EPHE, INSERM, Montpellier, France.
  • Delaunay T; IES, Université Montpellier, CNRS, Montpellier, France.
  • Glendenning E; Development, Regeneration and Neurophysiology, School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK.
  • Baxendale S; Development, Regeneration and Neurophysiology, School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK.
  • Liévens JC; MMDN, Université Montpellier, EPHE, INSERM, Montpellier, France.
  • Whitfield TT; Development, Regeneration and Neurophysiology, School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK.
  • Maurice T; MMDN, Université Montpellier, EPHE, INSERM, Montpellier, France.
  • Delprat B; MMDN, Université Montpellier, EPHE, INSERM, Montpellier, France.
Hum Mol Genet ; 31(16): 2711-2727, 2022 08 23.
Article in En | MEDLINE | ID: mdl-35325133
ABSTRACT
Wolfram syndrome (WS) is a rare genetic disease characterized by diabetes, optic atrophy and deafness. Patients die at 35 years of age, mainly from respiratory failure or dysphagia. Unfortunately, there is no treatment to block the progression of symptoms and there is an urgent need for adequate research models. Here, we report on the phenotypical characterization of two loss-of-function zebrafish mutant lines wfs1aC825X and wfs1bW493X. We observed that wfs1a deficiency altered the size of the ear and the retina of the fish. We also documented a decrease in the expression level of unfolded protein response (UPR) genes in basal condition and in stress condition, i.e. after tunicamycin treatment. Interestingly, both mutants lead to a decrease in their visual function measured behaviorally. These deficits were associated with a decrease in the expression level of UPR genes in basal and stress conditions. Interestingly, basal, ATP-linked and maximal mitochondrial respirations were transiently decreased in the wfs1b mutant. Taken together, these zebrafish lines highlight the critical role of wfs1a and wfs1b in UPR, mitochondrial function and visual physiology. These models will be useful tools to better understand the cellular function of Wfs1 and to develop novel therapeutic approaches for WS.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Wolfram Syndrome / Optic Atrophy Limits: Animals Language: En Journal: Hum Mol Genet Journal subject: BIOLOGIA MOLECULAR / GENETICA MEDICA Year: 2022 Document type: Article Affiliation country: Francia

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Wolfram Syndrome / Optic Atrophy Limits: Animals Language: En Journal: Hum Mol Genet Journal subject: BIOLOGIA MOLECULAR / GENETICA MEDICA Year: 2022 Document type: Article Affiliation country: Francia