PUBLICATION
Antioxidant treatment ameliorates phenotypic features of SMC1A-mutated Cornelia de Lange syndrome in vitro and in vivo
- Authors
- Cukrov, D., Newman, T., Leask, M., Leeke, B., Sarogni, P., Patimo, A., Kline, A.D., Krantz, I.D., Horsfield, J., Musio, A.
- ID
- ZDB-PUB-180604-2
- 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.
Citation
Cukrov, D., Newman, T., Leask, M., Leeke, B., Sarogni, P., Patimo, A., Kline, A.D., Krantz, I.D., Horsfield, J., Musio, A. (2018) Antioxidant treatment ameliorates phenotypic features of SMC1A-mutated Cornelia de Lange syndrome in vitro and in vivo. Human molecular genetics. 27(17):3002-3011.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping