Myocyte-mediated arginase expression controls hyperargininemia but not hyperammonemia in arginase-deficient mice.

ABSTRACT: Human arginase deficiency is characterized by hyperargininemia and infrequent episodes of hyperammonemia that cause neurological impairment and growth retardation. We previously developed a neonatal mouse adeno-associated viral vector (AAV) rh10-mediated therapeutic approach with arginase expressed by a chicken β-actin promoter that controlled plasma ammonia and arginine, but hepatic arginase declined rapidly. This study tested a codon-optimized arginase cDNA and compared the chicken β-actin promoter to liver- and muscle-specific promoters. ARG1(-/-) mice treated with AAVrh10 carrying the liver-specific promoter also exhibited long-term survival and declining hepatic arginase accompanied by the loss of AAV episomes during subsequent liver growth. Although arginase expression in striated mu

SUBMITTER: Hu C 

PROVIDER: S-EPMC4428413 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature