Lamin B1 Gene Expression in the Peripheral Nervous System of Mice with a Targeted Deletion of an Upstream Silencer

Autosomal Dominant Leukodystrophy (ADLD) is an ultra-rare neurological disorder that affects the white matter of the brain. Although publications have reported 33 families with over 70 ADLD-affected individuals, the exact prevalence of ADLD is unknown due to its rarity.1 The white matter of the brain and spinal cord is made up of bundles of axons, which are encased in an insulating coating called the myelin sheath. White matter functions as an insulating barrier to safeguard axons and enhance electrical signal transmission in the Central and Peripheral Nervous Systems (CNS and PNS). Complications involving cognitive function, balance, and mobility can result due to damage to white matter injury of the CNS. ADLD is inherited in an autosomal dominant manner and is caused by duplications of the LMNB1 gene. In rare cases, ADLD can result due to upstream deletions of the LMNB1 gene. In ADLD patients, normal cellular processes are disrupted in oligodendrocytes, a type of glial cell in the CNS that produces myelin. Because myelin is lost in ADLD patients, neurological symptoms such as impaired cognitive function, muscle stiffness, and motor dysfunction arise. Nmezi et al. (2023) demonstrated that the LMNB1 upstream regulatory region contains a novel silencer element that regulates lamin B1 expression in oligodendrocytes. The mouse strain Lmnb1-del-19 was generated that deleted the putative silencer element upstream of the LMNB1 gene to recapitulate the nature of the disease. Lmnb1 was overexpressed in oligodendrocytes obtained from these mice, but not in other types of CNS cells. The question remained whether the deletion of the silencer element affected the expression of lamin B1 in Schwann cells, which oversee the myelination of axons in the PNS. This project aimed to determine whether lamin B1 expression in the sciatic nerve, a peripheral nerve, was altered in Lmnb1-del-19 mice when compared to wild-type (WT) controls. Approximately four and seven-month-old Lmnb1-del-19