ZFIN ID: ZDB-PUB-180604-2
Antioxidant treatment ameliorates phenotypic features of SMC1A-mutated Cornelia de Lange syndrome in vitro and in vivo
Cukrov, D., Newman, T., Leask, M., Leeke, B., Sarogni, P., Patimo, A., Kline, A.D., Krantz, I.D., Horsfield, J., Musio, A.
Date: 2018
Source: Human molecular genetics   27(17): 3002-3011 (Journal)
Registered Authors: Horsfield, Jules
Keywords: none
MeSH Terms:
  • Animals
  • Antioxidants/pharmacology*
  • Biomarkers/analysis*
  • Cell Cycle Proteins/genetics*
  • Chromosomal Proteins, Non-Histone/genetics*
  • De Lange Syndrome/drug therapy*
  • De Lange Syndrome/genetics
  • De Lange Syndrome/pathology
  • Gene Expression Profiling
  • Gene Expression Regulation/drug effects*
  • Genomic Instability
  • Humans
  • In Vitro Techniques
  • Mutation*
  • Oxidative Stress/drug effects*
  • Zebrafish/genetics
  • Zebrafish/growth & development
PubMed: 29860495 Full text @ Hum. Mol. Genet.
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ABSTRACT
Cornelia de Lange syndrome (CdLS) is a rare disease characterized by cognitive impairment, multisystemic alterations, and premature aging. Furthermore, CdLS cells display gene expression dysregulation and genomic instability. Here, we demonstrated that treatments with the antioxidant drugs ascorbic acid and riboceine reduced the level of genomic instability and extended the in vitro lifespan of CdLS cell lines. We also found that antioxidant treatment partially rescued the phenotype of a zebrafish model of CdLS. Gene expression profiling showed that antioxidant drugs caused dysregulation of gene transcription; notably, a number of genes coding for the zinc finger (ZNF) containing Krueppel-associated box (KRAB) protein domain (KRAB-ZNF) were found to be down-regulated. Taken together, these data suggest that antioxidant drugs have the potential to ameliorate the developmental phenotype of CdLS.
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