Ainhoa Martínez-Pizarro, Sara Picó, Arístides López-Márquez, Claudia Rodriguez-López, Elena Montalvo, Mar Alvarez, Margarita Castro, Santiago Ramón-Maiques, Belén Pérez, José J Lucas, Eva Richard, Lourdes R Desviat
We have generated using CRISPR/Cas9 technology a partially humanized mouse model of the neurometabolic disease phenylketonuria (PKU), carrying the highly prevalent PAH variant c.1066-11G>A. This variant creates an alternative 3' splice site, leading to the inclusion of 9 nucleotides coding for 3 extra amino acids between Q355 and Y356 of the protein. Homozygous Pah c.1066-11A mice, with a partially humanized intron 10 sequence with the variant, accurately recapitulate the splicing defect and present almost undetectable hepatic PAH activity...
March 23, 2024: Human Molecular Genetics