ArticleThe Journal of biological chemistry2016
Novel Mouse Models of Methylmalonic Aciduria Recapitulate Phenotypic Traits with a Genetic Dosage Effect.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Clinical, phenotypic and genetic landscape of case reports with genetically proven inherited disorders of vitamin BCell reports. Medicine · 2022Pooled it
- Recent research advances in the biological function and molecular mechanism of methylmalonic acid.Journal of Zhejiang University. Science. B · 2025Review
- Animal models of methylmalonic acidemia: insights and challenges.Orphanet journal of rare diseases · 2025Review
- Article
- The bioactive sphingolipid playbook. A primer for the uninitiated as well as sphingolipidologists.Journal of lipid research · 2025Review
- Renal phenotyping in a hypomorphic murine model of propionic aciduria reveals common pathomechanisms in organic acidurias.Scientific reports · 2024Article
- Searching for homozygous haplotype deficiency in Manech Tête Rousse dairy sheep revealed a nonsense variant in the MMUT gene affecting newborn lamb viability.Genetics, selection, evolution : GSE · 2024Article
- Multiomic analysis in fibroblasts of patients with inborn errors of cobalamin metabolism reveals concordance with clinical and metabolic variability.EBioMedicine · 2024Article
- Using metabolic abnormalities of carriers in the neonatal period to evaluate the pathogenicity of variants of uncertain significance in methylmalonic acidemia.Frontiers in genetics · 2024Article
- Insights into energy balance dysregulation from a mouse model of methylmalonic aciduria.Human molecular genetics · 2023Article
- Biomarkers to predict disease progression and therapeutic response in isolated methylmalonic acidemia.Journal of inherited metabolic disease · 2023Review
- The impact of metabolic stressors on mitochondrial homeostasis in a renal epithelial cell model of methylmalonic aciduria.Scientific reports · 2023Article
- Article
- Mitochondrial disease, mitophagy, and cellular distress in methylmalonic acidemia.Cellular and molecular life sciences : CMLS · 2021Review
- Central nervous system-targeted adeno-associated virus gene therapy in methylmalonic acidemia.Molecular therapy. Methods & clinical development · 2021Article
- Decrease of disease-related metabolites upon fasting in a hemizygous knock-in mouse model (JIMD reports · 2021Article
- An expanding spectrum of complications in isolated methylmalonic aciduria.Journal of mother and child · 2020Review
- Biochemical and anaplerotic applications of in vitro models of propionic acidemia and methylmalonic acidemia using patient-derived primary hepatocytes.Molecular genetics and metabolism · 2020Article
- Impaired mitophagy links mitochondrial disease to epithelial stress in methylmalonyl-CoA mutase deficiency.Nature communications · 2020Article
- Pre-implantation genetic diagnosis in an Iranian family with a novel mutation in MUT gene.BMC medical genetics · 2020Article
Corrections and comments
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Authors and funding
19 authors at 11 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Methylmalonic aciduria (MMAuria), caused by deficiency of methylmalonyl-CoA mutase (MUT), usually presents in the newborn period with failure to thrive and metabolic crisis leading to coma or even death. Survivors remain at risk of metabolic decompensations and severe long term complications, notably renal failure and neurological impairment. We generated clinically relevant mouse models of MMAuria using a constitutive Mut knock-in (KI) allele based on the p.Met700Lys patient mutation, used homozygously (KI/KI) or combined with a knockout allele (KO/KI), to study biochemical and clinical MMAuria disease aspects. Transgenic Mut(ki/ki) and Mut(ko/ki) mice survive post-weaning, show failure to thrive, and show increased methylmalonic acid, propionylcarnitine, odd chain fatty acids, and sphingoid bases, a new potential biomarker of MMAuria. Consistent with genetic dosage, Mut(ko/ki) mice have lower Mut activity, are smaller, and show higher metabolite levels than Mut(ki/ki) mice. Further, Mut(ko/ki) mice exhibit manifestations of kidney and brain damage, including increased plasma urea, impaired diuresis, elevated biomarkers, and changes in brain weight. On a high protein diet, mutant mice display disease exacerbation, including elevated blood ammonia, and catastrophic weight loss, which, in Mut(ki/ki) mice, is rescued by hydroxocobalamin treatment. This study expands knowledge of MMAuria, introduces the discovery of new biomarkers, and constitutes the first in vivo proof of principle of cobalamin treatment in mut-type MMAuria.
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