Dr. Susan Hutson
Wake Forest University
Dr. Hutson and colleagues developed a mouse model of Classic MSUD with the aim of understanding the molecular basis for the effects of MSUD on the central nervous system and body metabolism. They previously generated a mouse containing a knockout (KO) of the mitochondrial branched chain aminotransferase (BCATm) enzyme. In this animal BCAA metabolism is blocked at the first step in all tissues outside the central nervous system. This animal provided evidence that branched chain amino acids (BCAAs) have profound effects on body metabolism, independent of their effects in brain and suggested the branched chain keto acids are the primary toxic metabolite in MSUD.