Rogerson, C;
Gissen, P;
(2018)
VPS33B and VIPAR are essential for epidermal lamellar body biogenesis and function.
Biochimica et Biophysica Acta - Molecular Basis of Disease
, 1864
(5(A))
pp. 1609-1621.
10.1016/j.bbadis.2018.01.028.
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Abstract
Mutations in VPS33B and VIPAS39 cause the severe multisystem disorder Arthrogryposis, Renal dysfunction and Cholestasis (ARC) syndrome. Amongst other symptoms, patients with ARC syndrome suffer from severe ichthyosis. Roles for VPS33B and VIPAR have been reported in lysosome-related organelle biogenesis, integrin recycling, collagen homeostasis and maintenance of cell polarity. Mouse knockouts of Vps33b or Vipas39 are good models of ARC syndrome and develop an ichthyotic phenotype. We demonstrate that the skin manifestations in Vps33b and Vipar deficient mice are histologically similar to those of patients with ARC syndrome. Histological, immunofluorescent and electron microscopic analysis of Vps33b and Vipar deficient mouse skin biopsies and isolated primary cells showed that epidermal lamellar bodies, which are essential for skin barrier function, had abnormal morphology and the localisation of lamellar body cargo was disrupted. Stratum corneum formation was affected, with increased corneocyte thickness, decreased thickness of the cornified envelope and reduced deposition of lipids. These defects impact epidermal homeostasis and lead to abnormal barrier formation causing the skin phenotype in Vps33b and Vipar deficient mice and patients with ARC syndrome.
| Type: | Article |
|---|---|
| Title: | VPS33B and VIPAR are essential for epidermal lamellar body biogenesis and function |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.bbadis.2018.01.028 |
| Publisher version: | https://doi.org/10.1016/j.bbadis.2018.01.028 |
| Language: | English |
| Additional information: | Copyright © 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/). |
| Keywords: | ARC syndrome, ARKID syndrome, CHEVI complex, Lamellar bodies, VIPAR, VPS33B |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10045433 |
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