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ENU mutagenesis identifies mice with mitochondrial branched-chain aminotransferase deficiency resembling human maple syrup urine disease
Genetic screening finds mice lacking a key mitochondrial enzyme similar to human maple syrup urine disease
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Abstract
Marked elevation of blood branched-chain amino acids (BCAAs) was observed in ENU-treated mice.
- Mice exhibited clinical features similar to human maple syrup urine disease (MSUD), despite normal BCKD genes and enzyme activity.
- Sequencing revealed a homozygous splice site mutation in the mitochondrial isoform of branched-chain aminotransferase (Bcat-2), leading to a deletion of exon 2.
- The mutation resulted in a significant reduction of Bcat-2 mRNA and a deficiency in both BCAT-2 protein and its enzyme activity.
- A BCAA-restricted diet improved clinical symptoms and normalized amino acid levels in affected mice.
- BCAT-2 deficiency in this mouse model may mimic human MSUD, offering insights into BCAA metabolism and toxicity.
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