Venditti, Charles (NHGRI)
Manoli, Eirini (Irini) (NHGRI)
Isolated Methylmalonic Acidemia (MMA) comprises a relatively common and heterogeneous group of inborn errors of metabolism. Most affected individuals display severe multisystemic disease characterized by metabolic instability, chronic renal disease, and neurological complications. Patients with the cobalamin A (cblA) subtype of MMA can have variable presentations, spanning the full spectrum of MMA associated symptoms and pathology, yet always harbor an element of clinical and biochemical responsiveness to injectable vitamin B12. NHGRI scientist have developed a model that would allow the testing of new therapies for cblA type MMA, and other forms of isolated MMA, they utilized homologous recombination to create a deletion allele of Mmaa, the enzyme that protects the enzyme methylmalonyl-CoA mutase, Mut, from oxidative inactivation. The NGHRI mouse model generated is severely affected but shows an element of vitamin B12 responsiveness which makes it useful for therapeutic studies in that an investigator can compare their intervention/results to that obtained with the vitamin cofactor as a control.
Useful for the study of new small molecule or mitochondrial based therapies for MMA, or more generally, therapies designed to improve mitochondrial function.
This mouse model is the first tractable animal model of cblA deficiency.