Albert Einstein College of Medicine researchers have engineered the first animal model of RNA polymerase III-related leukodystrophy. This rare but debilitating and poorly understood neurodegenerative disorder affects the myelin sheath that insulates nerves in the brain and spinal cord. The disorder mainly affects children, causing progressive impairment of cognitive and motor function and a broad spectrum of clinical abnormalities leading to premature death. The findings were published online on October 5 in the Proceedings of the National Academy of Sciences of the United States of America.

Disease-causing mutations occur in genes coding for different subunits of RNA polymerase III, an enzyme that synthesizes essential non-coding RNAs involved in protein synthesis and secretion, messenger RNA splicing, and other cellular functions. The Einstein team led by Ian Willis, Ph.D., and Robyn Moir, Ph.D., along with a doctoral student Emilio Merheb, introduced mutations into mice that caused hypomyelination and other disease features similar to those seen in patients. Examination of the mice revealed defects in the development and function of oligodendrocytes, the myelin-synthesizing cells of the central nervous system. This first mouse model of RNA polymerase III-related leukodystrophy will allow scientists to learn more about the disease and how it develops and enable potential treatments to be tested.

Dr. Willis is professor of biochemistry and of systems & computational biology at Einstein. Dr. Moir is associate research professor of biochemistry at Einstein. Mr. Merheb is a Ph.D. student in Dr. Willis’ lab.