Ldhb-flox Mouse

Ldhb, lactate dehydrogenase B, is a key enzyme in the glycolysis pathway. It reversibly catalyzes the conversion between pyruvate and lactate, with a higher affinity for lactate to convert it to pyruvate when oxygen is abundant [2]. This function is crucial for maintaining cellular energy metabolism and metabolite balance.

Ldhb has diverse effects on different biological processes and diseases. In classical swine fever virus (CSFV) infection, knockdown of Ldhb via interfering RNA induced mitochondrial fission and mitophagy, promoted NFKB signaling, inhibited apoptosis, and facilitated CSFV growth, while its overexpression decreased CSFV replication [1]. In leukemia, R-2-hydroxyglutarate attenuated aerobic glycolysis by suppressing the expression of Ldhb, among other genes [3]. In acetaminophen-induced liver injury, decreased SIRT1/PGC-1α/Ldhb expression was observed, and PGC-1α upregulation increased Ldhb synthesis, suggesting the PGC-1α/Ldhb axis as a potential therapeutic target [4]. In human pancreatic β cells, Ldhb limits lactate generation to maintain appropriate insulin release [5]. In hepatocellular carcinoma, DNMT3A-mediated epigenetic silencing of Ldhb contributed to HCC progression by remodeling the tumor immune microenvironment, and Ldhb may be a prognostic biomarker and therapeutic target [6]. In breast cancer, decreased Ldhb expression in tumor cells caused NK cell activation, and Ldhb is a promising target for activating the tumor immune microenvironment [7]. In ovarian cancer, Ldhb regulated histone lactylation on the PD-L1 promoter to promote its expression and immune escape [8]. In ischemic stroke, Ldhb-deficient mice showed increased neuronal survival due to elevated lactate-induced vasodilation [9]. In neurodegeneration, Ldhb deficiency in mice promoted mitochondrial dysfunction-mediated oxidative stress and neurodegeneration, and osmotin treatment could alleviate these effects [10].

In conclusion, Ldhb is essential for maintaining normal cellular metabolism and is involved in various disease processes such as viral infections, cancers, liver injury, ischemic stroke, and neurodegeneration. Gene knockout or knockdown models of Ldhb have been crucial in revealing its functions in these biological processes and disease conditions, providing potential therapeutic targets and insights into disease mechanisms.