Overlaps, gaps, and complexities of mouse models of Developmental and Epileptic Encephalopathy

Abstract

Mouse models have made innumerable contributions to understanding the genetic basis of neurological disease and pathogenic mechanisms and to therapy development. Here we consider the current state of mouse genetic models of Developmental and Epileptic Encephalopathy (DEE), representing a set of rare but devastating and largely intractable childhood epilepsies. By examining the range of mouse lines available in this rapidly moving field and by detailing both expected and unusual features in representative examples, we highlight lessons learned in an effort to maximize the full potential of this powerful resource for preclinical studies.

Keywords: Disease modeling; Epileptic encephalopathy; Mouse models; Seizure.

Fig. 1.

Functional annotation clustering of DEE genes by variant type. Visualization of enriched biological process Gene Ontology (GO) terms in two categories of genes – DEE genes with mostly or all LOF variants and DEE genes with only missense variants. Only GO terms with at least 5 genes in either category were included. Δ Log P-Value: difference in log p-value for clustering between the two gene categories; n: total number of genes in each category; k: number of genes in the total gene set annotated to the GO term.