Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2023

SLC13A5 in the human brain – lessons from in vitro model systems

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

Starfsvettvangur / Affiliations: 1. Háskóli Íslands, 2. Íslensk Erfðagreining

Kynnir / Presenter: Kristín Allison

Citrate transporter disorder (CTD) is a severe neurological disorder caused by recessive mutations in the SLC13A5 gene. One such mutation, G219R, has been found to be 25x more common in the Icelandic population than the rest of the world. The symptoms seen in CTD in humans include severe epilepsy, ataxia, hypotonia and lack of speech. In experimental animal models however, the gene can be knocked out without deleterious effects, highlighting the need for a human-based model system.
Currently, there is no effective treatment for CTD and due to the lack of previous research on the role of citrate transport in the human brain, determining the reasons for the severe phenotype seen in CTD is extremely challenging.
The project presented here was put together as an effort to elucidate the role of citrate transport in the human brain. The first part of the project involved immunostaining human brain tissue samples from non-affected individuals, to determine the localization of the protein on a tissue scale as well as on the cellular level. Using this information as a roadmap, I then generated in vitro model systems utilizing patient-derived iPSCs and an isogenic control line to test hypotheses on cell types generated through neural induction and differentiation.
Here, I will present the latest results from these systems, obtained through analysing differences in cell morphology, synapse formation, neuronal outgrowth and activity, as well as relevant biochemical processes.