Propionyl-CoA Carboxylase Beta (PCCB) Alleles in Propionic Acidemia (PA) mouse models

Description:

Propionic acidemia (PA) is an autosomal recessive metabolic disorder caused by mutations in either Propionyl-CoA carboxylase alpha (PCCA) or Propionyl-CoA carboxylase beta (PCCB). The products of these genes form the alpha and beta subunits of the enzyme propionyl-Co A carboxylase (PCC), a critically important mitochondrial enzyme involved in the catabolism of branched chain amino acids. NHGRI scientist have developed new mouse models that recapitulate the human clinical phenotype of severe propionic acidemia caused by PCCB deficiency, namely neonatal lethality and increased propionyl-CoA derived metabolites. These new PCCB alleles are the first described and can be used to model the spectrum of clinically important features of PA, and support testing of new treatments, including adeno-associated virus (AAV) gene therapy, mRNA therapy, genome editing, base editing, mRNA editing, small molecules, enzyme replacement therapy, and microbiome targeted therapies.