Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2021

Erindi/veggspjald / Talk/poster E74

Generating iPSC-derived disease models to analyze the causes of neurological symptoms in CTD

Höfundar / Authors: Kristín Allison, Helgi J. Ísaksson, Sigríður Rut Franzdóttir

Starfsvettvangur / Affiliations: Háskóli Íslands

Kynnir / Presenter: Kristín Allison

Citrate transporter disorder (CTD) is a severe neurological disorder caused by mutations in the SCL13A5 gene. The gene encodes a sodium-dependent citrate transporter (NaCT) and the disease is characterized by severe epilepsy, hypotonia, ataxia and lack of speech. The causative link between the mutations and symptoms has not been explained and little is known about the role of citrate and citrate transport in the human brain. As no data exists on the distribution of the NaCT protein within the human brain, the starting point for this project is a detailed protein expression analysis using sections from biobanked human brain tissue. Immunostaining for the NaCT protein and co-staining with various CNS markers enables us to reveal which brain areas and cell types are likely to play a role in the disease aetiology. The information gleaned from the expression analysis will serve as a foundation for the generation of in vitro model systems. For the models, we are currently using induced pluripotent stem cells (iPSCs) from patients and isogenic controls, as well as an edited commercial line, to derive the cell types deemed relevant according to the expression analysis and disease phenotype. Here, I will present the initial findings of the expression analysis and some of our hypotheses, as well as the ongoing development of the in vitro model systems.