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IVANA PIBIRI

RESCUE OF LRBA GENE EXPRESSION IN PRIMARY HUMAN FIBROBLASTS CHARACTERISED BY NONSENSE MUTATION c. 5047 (C>T).

  • Authors: Riccardo PERRIERA, Federica CORRAO, Ivana PIBIRI, Andrea PACE, Laura LENTINI
  • Publication year: 2021
  • Type: Abstract in atti di convegno pubblicato in rivista
  • OA Link: http://hdl.handle.net/10447/556180

Abstract

Primary immunodeficiencies (PIDs) are rare genetic diseases characterized by susceptibility to infections, increased risk of autoimmunity, hypogammaglobulinemia, and lymphoproliferative syndromes. PIDs are associated to genetic alterations in about 400 known genes, among which, mutations of the LRBA gene. LRBA gene encodes a widely expressed multi-domain protein with highly conserved BEACH domain, involved in regulation of endosomal trafficking, particularly endocytosis of ligand-activated receptors. It was reported that stop mutations affect this gene leading to the loss of the protein expression. Recently, we identified three Translational Readthrough Inducing Drug (TRID), that showed high readthrough activity in cystic fibrosis nonsense model systems, in this study we tested one of our TRIDs in a LRBA model system. To evaluate the readthrough activity of the TRID molecule in the rescue of the LRBA expression in human primary fibroblasts characterized by an homozygous stop mutation, we treated LRBAstop cells with compound 1 after 24, 48 and 72 hours of treatment. The expression of the LRBA gene was analyzed by Real time RT-PCR and Western blot analyses. LRBA expression resulted increased after 72-hours of chronic treatment with our TRID molecule and the cells showed to growth normally. Our results confirmed that compound 1 is able to promote the readthrough of premature stop codon, besides in CF model systems, also in a different genetic context such as in LRBA expression.