Ricerc@Sapienza

Progeroid syndromes induced by mutations in lamin A or in its interactors – named progeroid laminopathies – are model systems for the dissection of the molecular pathways causing physio- logical and premature aging. A large amount of data, based mainly on the Hutchinson Gilford Progeria syndrome (HGPS), one of the best characterized progeroid laminopathy, has highlighted the role of lamins in multiple DNA activities, including replication, repair, chromatin organization and telomere function.

The Schimke immuno-osseous dysplasia is an autosomal recessive genetic osteochondrodysplasia characterized by dysmorphism, spondyloepiphyseal dysplasia, nephrotic syndrome and frequently T cell immunodeficiency. Several hypotheses have been proposed to explain pathophysiology of the disease, however, the mechanism by which SMARCAL1 mutations cause the syndrome is elusive. Here, we generated a conditional SMARCAL1 knockdown model in iPSCs to mimic conditions associated with the severe form the disease.