To create a model of intermediate MSUD, we used a transgenic strategy to express human E2 in the liver of E2 knockout mice. As mentioned above, E2 knockouts without transgene derived E2 die during the early neonatal period. We show that expression of a human E2 transgene in the liver of these knockout mice is able to rescue the neonatal lethality. Many of the rescue mice survived to adulthood. It is interesting to note that in these mouse lines only ~5–6% of normal BCKDH activity in the liver was sufficient to allow survival. We also demonstrated that BCAA levels in blood of these rescue mice were intermediate between controls and knockouts. The hallmarks of intermediate MSUD human patients are persistently increased levels of BCAA and BCKDH activity in the range of 3–30% of normal [1]. Because of the phenotypic similarities of the rescue mice to the human patients, these genetically engineered mice represent a useful small animal model of the intermediate form of MSUD.