176. An Internally Tagged Methylmalonyl-CoA Mutase (Mut) Displays In Vivo Activity after AAV9 Mediated Gene Delivery

Methylmalonic acidemia (MMA) is an autosomal recessive metabolic disorder most frequently resulting from mutations in the mitochondrial localized enzyme, methylmalonyl-CoA mutase (MUT). A mouse model replicating the most severe form of MMA in which there is complete loss of Mut expression (Mut-/-) displays neonatal lethality but has been successfully used to demonstrate proof-of-principle for gene therapy using AAV vectors. To model the hepato-, renal and cerebral manifestations of MMA, we have generated several lines of transgenic/knock-out mice to create viable animal models of MMA.