Epigenetic disorders: Lessons from the animals-animal models in chromatinopathies

Abstract

Chromatinopathies are defined as genetic disorders caused by mutations in genes coding for protein involved in the chromatin state balance. So far 82 human conditions have been described belonging to this group of congenital disorders, sharing some molecular features and clinical signs. For almost all of these conditions, no specific treatment is available. For better understanding the molecular cascade caused by chromatin imbalance and for envisaging possible therapeutic strategies it is fundamental to combine clinical and basic research studies. To this end, animal modelling systems represent an invaluable tool to study chromatinopathies. In this review, we focused on available data in the literature of animal models mimicking the human genetic conditions. Importantly, affected organs and abnormalities are shared in the different animal models and most of these abnormalities are reported as clinical manifestation, underlying the parallelism between clinics and translational research.

Keywords: Danio rerio; animal models; chromatinopathies; drosophila melanogaster; mus musculus; rare diseases.

FIGURE 1

Schematic representation of effects on chromatin equilibrium for RSTS, KLEFS and KS syndromes. The drawing shows the impact of abnormal function of proteins coded by different genes having common effects on chromatin state equilibrium.

FIGURE 2

Genetic convergence for different human phenotype. In (A), canonical and non-canonical causative genes are shown for RSTS, CdLS and KS. In (B) a schematic representation of the hypothesis of possible shared molecular pathways upon chromatin balance disruption resulting in organ abnormal development that could be studied combining animal models and human data.

FIGURE 3

Function or organ found impaired or altered in animal models of chromatinopathies. Genes coding for writers (green), erasers (blue), readers (pink) and remodelers (orange), for which haploinsufficiency results in human abnormalities. (A) reports functions/organs in animal models altered in more than 20% of analyzed genes and (B) those in <20%.