In-depth phenotyping reveals common and novel disease symptoms in a hemizygous knock-in mouse model (Mut-ko/ki) of mut-type methylmalonic aciduria

Lucienne, Marie; Aguilar-Pimentel, Juan Antonio; Amarie, Oana V; Becker, Lore; Calzada-Wack, Julia; da Silva-Buttkus, Patricia; Garrett, Lillian; Hölter, Sabine M; Mayer-Kuckuk, Philipp; Rathkolb, Birgit; Rozman, Jan; Spielmann, Nadine; Treise, Irina; Busch, Dirk H; Klopstock, Thomas; Schmidt-Weber, Carsten; Wolf, Eckhard; Wurst, Wolfgang; Forny, Merima; Mathis, Déborah

doi:10.1016/j.bbadis.2019.165622

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Lucienne, M., Aguilar-Pimentel, J. A., Amarie, O. V., Becker, L., Calzada-Wack, J., da Silva-Buttkus, P., Garrett, L., Hölter, S. M., Mayer-Kuckuk, P., Rathkolb, B., Rozman, J., Spielmann, N., Treise, I., Busch, D. H., Klopstock, T., Schmidt-Weber, C., Wolf, E., Wurst, W., Forny, M., … Baumgartner, M. R. (2019). In-depth phenotyping reveals common and novel disease symptoms in a hemizygous knock-in mouse model (Mut-ko/ki) of mut-type methylmalonic aciduria. Biochimica et Biophysica Acta. Molecular Basis of Disease, 165622. https://doi.org/10.1016/j.bbadis.2019.165622

Abstract

Isolated methylmalonic aciduria (MMAuria) is primarily caused by deficiency of methylmalonyl-CoA mutase (MMUT or MUT). Biochemically, MUT deficiency results in the accumulation of methylmalonic acid (MMA), propionyl-carnitine (C3) and other metabolites. Patients often exhibit lethargy, failure to thrive and metabolic decompensation leading to coma or even death, with kidney and neurological impairment frequently identified in the long-term. Here, we report a hemizygous mouse model which combines a knock-in (ki) missense allele of Mut