Lgi2-flox Mouse

Lgi2, or leucine-rich, glioma inactivated 2, belongs to a family encoding secreted, beta-propeller domain proteins with EPTP/EAR epilepsy-associated repeats. It acts on metalloproteinase-lacking members of the ADAM family of neuronal receptors, functioning in synapse remodeling. LGI2, like LGI1, is neuronally secreted and ensures electrical stability during the early post-natal pruning period of the brain [1,3,4].

A protein-truncating mutation in the Lgi2 gene was identified in a large Lagotto romagnolo canine pedigree with a remitting focal epilepsy. The epilepsy in these dogs onsets at around seven weeks (equivalent to human two years) and remits by four months (human eight years). LGI2 is highly expressed in the immediate post-natal period until halfway through pruning, acting at least in part through the same ADAM receptors as LGI1 but earlier. This suggests LGI2 should be considered a candidate gene for common remitting childhood epilepsies, and the LGI2-to-LGI1 transition could be relevant for understanding childhood epilepsy remission mechanisms [1]. Also, LGI2 is a candidate gene for partial epilepsy with pericentral spikes (PEPS) based on protein sequence analysis and patient-specific chromosomal deletions [2].

In conclusion, Lgi2 plays a crucial role in synapse remodeling and ensuring electrical stability during early brain development. Studies on Lgi2 in canine models have revealed its potential significance in understanding and treating common remitting childhood epilepsies and related epilepsy phenotypes like PEPS.