| First Author | Teng XY | Year | 2022 |
| Journal | FASEB J | Volume | 36 |
| Issue | 3 | Pages | e22212 |
| PubMed ID | 35167164 | Mgi Jnum | J:378819 |
| Mgi Id | MGI:7355066 | Doi | 10.1096/fj.202101652R |
| Citation | Teng XY, et al. (2022) A novel Lgi1 mutation causes white matter abnormalities and impairs motor coordination in mice. FASEB J 36(3):e22212 |
| abstractText | Leucine-rich glioma-inactivated protein 1 (LGI1) is known to play a key role in autosomal dominant lateral temporal lobe epilepsy (ADLTE). The ADLTE is an inherited disease characterized by focal seizures with distinctive auditory or aphasic symptoms. A large number of mutations on the Lgi1 gene have been reported and are believed to be the genetic cause for ADLTE. We identified a novel missense mutation, c.152A>G (p.Asp51Gly), on Lgi1 from a Chinese ADLTE patient who manifests locomotor imbalance and white matter reduction. However, it remains unknown how mutant LGI1 causes white matter abnormalities at molecular and cellular levels. Here, we generated a knock-in mouse bearing this Lgi1 mutation. We found that Lgi1(D51G) (/) (D51G) mice exhibited impaired defective white matter and motor coordination. We observed that Lgi1(D51G) (/) (D51G) mice displayed a reduced number of mature oligodendrocytes (OLs) and deficient OL differentiation in the white matter. However, the population of oligodendrocyte precursor cells was not affected in Lgi1(D51G) (/) (D51G) mice. Mechanistically, we showed that the Lgi1(D51G) mutation resulted in altered mTOR signaling and led to decreased levels of Sox10. Given that Sox10 is a key transcriptional factor to control OL differentiation, our results strongly suggest that the Lgi1(D51G) mutation may cause white matter abnormalities via inhibiting Sox10-dependent OL differentiation and myelination in the central nervous system. |
