Lgi1, or Leucine-rich glioma-inactivated protein 1, is a secreted glycoprotein mainly expressed in the brain, playing a crucial role in central nervous system development and physiology. It is associated with pathways related to myelination, synaptic transmission, and regulation of neuronal activity. Mutations or auto-antibodies against LGI1 are linked to autosomal dominant lateral temporal lobe epilepsy (ADLTE) and autoimmune encephalitis respectively, highlighting its importance in maintaining normal brain function [2].

Conditional knockout (cKO) of Opalin, an identified LGI1 receptor on oligodendrocytes (OLs), caused hypomyelination and white matter abnormalities, phenocopying LGI1 deficiency in mice. This indicates that the LGI1/OPALIN complex is vital for OL differentiation and myelination [1]. Knock-down of LGI1 in rodents revealed its necessity for normal brain development. In mature brains, it associates with Kv1 channels and AMPA receptors, regulating their expression and function, and its loss-of-function is a common feature in the genesis of epileptic seizures in ADLTE and anti-LGI1 autoimmune encephalitis [2].

In summary, Lgi1 is essential for normal brain development, myelination, and regulation of synaptic transmission. Studies using KO/CKO mouse models have significantly contributed to understanding its role in diseases such as epilepsy and autoimmune encephalitis, providing insights into the underlying molecular mechanisms and potential therapeutic targets.

References:

1. Teng, Xiao-Yu, Hu, Ping, Zhang, Cai-Ming, Chen, Guiquan, Shi, Yun Stone. 2024. OPALIN is an LGI1 receptor promoting oligodendrocyte differentiation. In Proceedings of the National Academy of Sciences of the United States of America, 121, e2403652121. doi:10.1073/pnas.2403652121. https://pubmed.ncbi.nlm.nih.gov/39083419/

2. Baudin, Paul, Cousyn, Louis, Navarro, Vincent. 2021. The LGI1 protein: molecular structure, physiological functions and disruption-related seizures. In Cellular and molecular life sciences : CMLS, 79, 16. doi:10.1007/s00018-021-04088-y. https://pubmed.ncbi.nlm.nih.gov/34967933/