Kmo-flox Mouse

Kmo, short for kynurenine-3-monooxygenase, is a mitochondrial enzyme. It is a key rate-limiting enzyme in the eukaryotic kynurenine pathway (KP), which is the major catabolic route of tryptophan. Kmo can convert kynurenine into the neurotoxin 3-hydroxykynurenine and quinolinic acid, influencing the balance of toxic and neuroprotective metabolites in the body [1].

In various disease models, the role of Kmo has been explored. In myocardial ischemia (MI) mouse models, pharmacological or heart-specific inhibition of Kmo suppressed the elevation of xanthurenic acid (XA) and ameliorated OGD-induced cardiomyocytes injury and ligation-induced MI injury, by maintaining mitochondrial fusion and fission balance [2]. In hepatocellular carcinoma (HCC) cell experiments, low expression of Kmo promoted HCC proliferation, invasion, metastasis, EMT, and cell apoptosis [3]. In atherosclerotic plaque studies, lentivirus-mediated KMO silencing in high-fat-fed ApoE-/-mice attenuated plaque formation and promoted plaque stability [4]. In a stroke mouse model, suppression of Kmo expression by circSCMH1 enhanced mitochondrial fusion and inhibited mitophagy, promoting post-stroke brain repair [5]. In kmo-/-mice, they were vulnerable to pathogenic viral challenge, indicating Kmo and its enzymatic product QUIN have antiviral functions [6]. Inhibition of Kmo may also mitigate colitis and protect against colorectal cancer [7]. In Huntington's disease (HD) model systems, inhibition of Kmo shifted the flux in the KP towards the formation of the neuroprotectant kynurenic acid (KYNA), ameliorating disease-relevant phenotypes [8].

In conclusion, Kmo is a crucial enzyme in the kynurenine pathway, significantly affecting multiple biological processes and disease conditions. Studies using gene knockout or conditional knockout mouse models have revealed its roles in diseases such as myocardial ischemia, hepatocellular carcinoma, atherosclerotic plaque instability, stroke, viral infections, colitis, colorectal cancer, and Huntington's disease. These findings provide potential therapeutic directions for these diseases by targeting Kmo.