Homozygous inactivation of the LGI1 gene results in hypomyelination in the peripheral and central nervous systems.

Mutations in the LGI1 gene in humans predispose to the development of autosomal dominant partial epilepsy with auditory features (ADPEAF). Homozygous inactivation of the Lgi1 gene in mice results in an epilepsy phenotype characterized by clonic seizures within 2-3 weeks after birth. Before onset of seizures, the 2-3-week-old null mutant mice show poor locomotor activity and neuromuscular strength. EM analysis of the sciatic nerve demonstrates impaired myelination of axons in the peripheral nervous system. Although heterozygous mutant mice do not show any locomotor phenotypes, they also demonstrate an intermediate level of hypomyelination compared with the wild-type mice. Hypomyelination was also observed in the central nervous system, which, although relatively mild, was still significantly different from that of the wild-type mice. These data suggest a role for LGI1 in the myelination functions of Schwann cells and oligodendrocytes.