B6-Mmut*M698K/Mmut KO Mouse
Product Name
B6-Mmut*M698K/Mmut KO Mouse
Product ID
C001828
Strain Name
C57BL/6JCya-Mmutem1/Mmutem2(M698K)/Cya
Backgroud
C57BL/6JCya
Status
When using this mouse strain in a publication, please cite “B6-Mmut*M698K/Mmut KO Mouse (Catalog C001828) were purchased from Cyagen.”
Product Type
Age
Genotype
Sex
Quantity
Gene Name
Gene Alias
Mcm, Mut, D230010K02Rik
NCBI ID
Chromosome
Chr 17
MGI ID
Datasheet
Strain Description
The Mmut gene encodes the mitochondrial enzyme methylmalonyl-CoA mutase (MCM), a protein critical for the metabolism of specific amino acids and fatty acids, cholesterol catabolism, and energy production. This gene is widely expressed, with particularly high levels in the liver and kidney. Mutations in Mmut cause methylmalonic acidemia (MMA), a severe autosomal recessive genetic disorder characterized by the accumulation of methylmalonic acid in blood and urine, which triggers life-threatening metabolic crises, developmental delay, and progressive renal failure. The refractoriness of this condition to conventional dietary and pharmacological management has led some patients to undergo elective liver transplantation (LT) or combined liver-kidney transplantation (LKT) to maintain metabolic stability. While LT or LKT reduces the risk of metabolic decompensation, post-transplant patients still exhibit biochemical abnormalities such as elevated methylmalonic acid levels in blood and cerebrospinal fluid. Patients receiving liver transplantation alone remain at risk of renal insufficiency, basal ganglia damage, and optic neuropathy. Additionally, long-term immunosuppressive therapy post-transplant may induce toxic reactions and increase the risk of malignancy [1-2]. Current therapeutic strategies for MMA focus on developing drugs that enhance MCM activity or bypass metabolic blocks, including chaperone therapy to improve protein folding and stability, enzyme replacement therapy, and gene therapy strategies to deliver functional Mmut gene copies [3-4].
B6-Mmut*M698K/Mmut KO mice are a MMA disease model generated by crossing Mmut-knockout mice (with exon 3 deleted) with Mmut-mutant mice (carrying the p.M698K mutation in exon 12). Homozygous deletion of the gene results in embryonic lethality, and homozygous mutant mice die within 1 day of birth. The p.M698K (ATG to AAG) mutation carried by B6-Mmut*M698K/Mmut KO mice is equivalent to the p.M700K (ATG to AAG) mutation in the human MMUT gene. This model can be used to study the pathogenic mechanisms and therapeutic approaches for MMA.
Reference
Head PE, Meier JL, Venditti CP. New insights into the pathophysiology of methylmalonic acidemia. J Inherit Metab Dis. 2023 May;46(3):436-449.
Baumgartner MR, Hörster F, Dionisi-Vici C, Haliloglu G, Karall D, Chapman KA, Huemer M, Hochuli M, Assoun M, Ballhausen D, Burlina A, Fowler B, Grünert SC, Grünewald S, Honzik T, Merinero B, Pérez-Cerdá C, Scholl-Bürgi S, Skovby F, Wijburg F, MacDonald A, Martinelli D, Sass JO, Valayannopoulos V, Chakrapani A. Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia. Orphanet J Rare Dis. 2014 Sep 2;9:130.
Haijes HA, van Hasselt PM, Jans JJM, Verhoeven-Duif NM. Pathophysiology of propionic and methylmalonic acidemias. Part 2: Treatment strategies. J Inherit Metab Dis. 2019 Sep;42(5):745-761.
Venturoni LE, Venditti CP. Treatment of metabolic disorders using genomic technologies: Lessons from methylmalonic acidemia. J Inherit Metab Dis. 2022 Sep;45(5):872-888.
Strain Strategy
The exon 3 region of the mouse Mmut gene is knocked out using gene editing technology.
The p.M698K (ATG to AAG) mutation is introduced into exon 12 of the mouse Mmut gene using gene editing technology.
Figure 1. Gene editing strategy for Mmut knockout (Mmut KO) mice.
Figure 2. Gene editing strategy for Mmut mutant mice (Mmut*M698K).
Application Area
Research on the pathogenic mechanisms and therapeutic approaches of methylmalonic acidemia (MMA);
Research on the mechanisms of other mitochondrial metabolic diseases;
Research on the mechanisms of neurological damage;
Research on the mechanisms and therapeutic strategies of kidney diseases.
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