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Comparative analysis of DEE model brain transcriptomes

ABSTRACT: Developmental and epileptic encephalopathy (DEE) caused by rare mutations in 118 different genes leads to profound disability and seizures starting in infancy. To generate models of developmental and epileptic encephalopathy, we used CRISPR/Cas9 to knock down 2 causative genes, ap3b2 (DEE48) and eef1a2(DEE33) in Xenopus laevis tadpoles and confirmed editing and seizure-like behaviours. We then analysed the brains of these tadpoles using transcriptomics, to see how development is changed by loss of function of these genes. We found that many genes associated with GABA signalling, Na and Ca2+ ion transport, axon guidance, dendrite development and transport across the blood brain barrier and are down regulated in both models compared to controls. This shows how DEE caused by loss of fuction of different genes that do not code for known functionally linked proteins can lead to similar brain developmental phenotypes and seizure suceptibility.

ORGANISM(S): Xenopus laevis

PROVIDER: GSE312492 | GEO | 2025/12/29

REPOSITORIES: GEO

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