Mmut P.R106C/P.R106C Knock-In Methylmalonyl-CoA Mutase (Mmut) Allele mouse models for the Study of Methylmalonic Acidemia (MMA)

Isolated Methylmalonic Acidemia (MMA) comprises a relatively common and heterogeneous group of inborn errors of metabolism. In order to create mouse models of MMA to resemble the pathogenic mutations seen in patients, the NHGRI scientist used genome editing to generate new mutants of the Mmut allele - p.R106C. This allele recapitulates a missense mutation seen in multiple patients with the disorder. Of note and emphasis is the fact that there are no transgene cassettes or other alternations to the Mmut locus in these new mouse models. These mice display elevations of MMA biomarkers, such as 2-methylcitrate, are viable, without obvious gross pathology, and fully fertile, they can be easily bred. These new models can be used for physiology studies, biomarker discovery, and to test the effects of gene therapy, cell therapy, mRNA therapy, nucleic acid therapies, small molecules, the microbiome, and especially genome editing using AAV, Cas/CRISPR, and other editing approaches as treatments for MMA and related conditions.