Höfundar:
Kristín Allison, Helgi J. Ísaksson, Guðmundur Norðdahl, Sigríður Rut Franzdóttir
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 almost 50x more common in the Icelandic population than the rest of the world.
The SLC13A5 gene encodes a sodium-coupled citrate transporter (NaCT), the orthologue of which can be knocked out in experimental animals without deleterious neurological effects. The neurological symptoms seen in CTD in humans include severe epilepsy, ataxia, hypotonia and lack of speech. This highlights a need for a human-based model system for CTD.
The project presented here began with a histological analysis of human brain samples from non-affected individuals. We examined several brain areas, determining the localization of the protein on a tissue scale as well as on the cellular level. This information is then used as a guide in the generation and utilization of in vitro model systems.
For the model systems I use patient-derived iPS cells and an isogenic control line to test hypotheses on cell types generated through neural induction and differentiation. We analyze differences in cell morphology, neuronal outgrowth and biochemical processes and have generated co-cultures to examine the interplay between these cells.