Category: Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL)

Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) is a rare disorder that affects the white matter in the brain and spinal cord, usually appearing in childhood or adolescence. Symptoms include loss of coordination and difficulty walking. LBSL is caused by mutations in the DARS2 gene, which produces an enzyme necessary for making mitochondrial proteins.

Most patients have two different mutations in the DARS2 gene: one common mutation that creates a shortened protein and another variable mutation that changes a single amino acid. These mutations impact the brain and spine the most, but the exact mechanisms of how they cause the disease are unknown.

To study LBSL and find potential treatments, researchers have created two mouse models that mimic the genetic traits seen in LBSL patients using CRISPR/Cas9 gene editing. These models include a DARS2 knockout and a DARS2 missense mutation. These mouse models are designed to closely resemble the genetic profile of LBSL patients, helping researchers understand the disease better. The research involves characterizing these mouse models to uncover the cellular and molecular mechanisms of the disease. This includes evaluating motor skills, examining brain and spine tissue, and analyzing gene expression and protein levels. This research is crucial for understanding LBSL and developing effective treatments to improve patients’ lives. By studying these mouse models, we hope to unravel the underlying mechanisms of LBSL and identify potential targets for future therapies.