Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/168234
Title: Comparison of zebrafish and mice knockouts for Megalencephalic Leukoencephalopathy proteins indicates that GlialCAM/MLC1 forms a functional unit
Author: Pérez Rius, Carla
Folgueira, Mónica
Elorza-Vidal, Xabier
Alia, Alia
Hoegg-Beiler, Maja B.
Eeza, Muhamed N.H.
Díaz, María Luz
Nunes Martínez, Virginia
Barrallo-Gimeno, Alejandro
Estévez Povedano, Raúl
Keywords: Proteïnes
Encefalitis
Ratolins (Animals de laboratori)
Proteins
Encephalitis
Mice (Laboratory animals)
Issue Date: 21-Nov-2019
Publisher: BioMed Central
Abstract: Background: Megalencephalic Leukoencephalopathy with subcortical Cysts (MLC) is a rare type of leukodystrophy characterized by astrocyte and myelin vacuolization, epilepsy and early-onset macrocephaly. MLC is caused by mutations in MLC1 or GLIALCAM, coding for two membrane proteins with an unknown function that form a complex specifically expressed in astrocytes at cell-cell junctions. Recent studies in Mlc1-/- or Glialcam-/- mice and mlc1-/- zebrafish have shown that MLC1 regulates glial surface levels of GlialCAM in vivo and that GlialCAM is also required for MLC1 expression and localization at cell-cell junctions. Methods: we have generated and analysed glialcama-/- zebrafish. We also generated zebrafish glialcama-/- mlc1-/- and mice double KO for both genes and performed magnetic resonance imaging, histological studies and biochemical analyses. Results: glialcama-/- shows megalencephaly and increased fluid accumulation. In both zebrafish and mice, this phenotype is not aggravated by additional elimination of mlc1. Unlike mice, mlc1 protein expression and localization are unaltered in glialcama-/- zebrafish, possibly because there is an up-regulation of mlc1 mRNA. In line with these results, MLC1 overexpressed in Glialcam-/- mouse primary astrocytes is located at cell-cell junctions. Conclusions: this work indicates that the two proteins involved in the pathogenesis of MLC, GlialCAM and MLC1, form a functional unit, and thus, that loss-of-function mutations in these genes cause leukodystrophy through a common pathway.
Note: Reproducció del document publicat a: https://doi.org/10.1186/s13023-019-1248-5
It is part of: Orphanet Journal of Rare Diseases, 2019, vol. 14, num. 1, p. 268
URI: http://hdl.handle.net/2445/168234
Related resource: https://doi.org/10.1186/s13023-019-1248-5
ISSN: 1750-1172
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Fisiològiques)

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