Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2019

Erindi/veggspjald / Talk/poster E53

A disease model under construction: following SLC13A5 around the brain

Höfundar / Authors: Kristín Allison, Helgi J. Ísaksson, Guðmundur L. Norðdahl, Sigríður R. Franzdóttir

Starfsvettvangur / Affiliations: Háskóli Íslands, Íslensk Erfðagreining

Kynnir / Presenter: Kristín Allison

Citrate transporter disorder (CTD) is a rare, recently discovered neurological disorder caused by recessive mutations in the SLC13A5 gene, which encodes a citrate transporter protein (NaCT). We have found a known disease-causing mutation to be highly prevalent in Iceland compared to the rest of Europe, pointing to a founder effect. This led to the initiation of a new project, aiming to create a cell culture disease model to mimic the effects of NaCT dysfunction on the human CNS.
As no data exists on the distribution of the NaCT protein within the human brain, we set out to perform expression analysis on sections from bio-banked 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. This information then serves as the foundation for our in vitro model.
For the disease model we use induced pluripotent stem cells (iPSCs), which can be differentiated into various cell types. Thus, patient derived iPSCs can be used to model different CNS cell types under disease conditions, and as CTD symptoms can vary between individuals, we can account for effects of the genetic background. By employing CRISPR-Cas9 editing, disease mutations will be reversed in patient derived iPSCs and introduced into control iPSC lines for genetically identical pairs. Here, we provide an overview of the project, the disorder and present our initial findings.