A novel Pah-exon1 deleted murine model of phenylalanine hydroxylase (PAH) deficiency.

ABSTRACT: Phenylalanine hydroxylase (PAH) deficiency, colloquially known as phenylketonuria (PKU), is among the most common inborn errors of metabolism and in the past decade has become a target for the development of novel therapeutics such as gene therapy. PAH deficient mouse models have been key to new treatment development, but all prior existing models natively express liver PAH polypeptide as inactive or partially active PAH monomers, which complicates the experimental assessment of protein expression following therapeutic gene, mRNA, protein, or cell transfer. The mutant PAH monomers are able to form hetero-tetramers with and inhibit the overall holoenzyme activity of wild type PAH monomers produced from a therapeutic vector. Preclinical therapeutic studies would benefit from a PKU model that

SUBMITTER: Richards DY 

PROVIDER: S-EPMC8173763 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature