Ldha-flox Mouse

Lactate dehydrogenase A (LDHA), also known as LDH5, is a crucial enzyme in aerobic glycolysis. It catalyzes the final step of glycolysis, converting pyruvate to lactate. This process is significant as most cancer cells rely on enhanced tumor glycolysis to meet their energy demands, with LDHA playing a key role in this metabolic reprogramming [1]. Additionally, it is involved in lactate shuttle and symbiosis in cancer cells, which impacts prognosis.

CM-specific LDHA knockout mice showed inhibited cardiomyocyte proliferation, leading to worse cardiac function and lower survival rate in the neonatal apical resection model. In contrast, CM-specific overexpression of LDHA promoted cardiomyocyte proliferation and cardiac repair post-MI, indicating its role in cardiac repair [2]. MK/platelet-specific LdhA knockout mice had an increased number of platelets with accelerated MK maturation and proplatelet formation, suggesting a non-classical function of LDHA in translation that could be a target for thrombocytopenia therapy [3]. In human trophoblast cells, LDHA knockdown induced G0/G1 phase arrest and increased apoptosis, while overexpression reversed these effects, revealing a new regulatory pathway for LDHA/PI3K/AKT/FOXO1/CyclinD1 in trophoblast cell cycle and proliferation [4].

In conclusion, LDHA is essential for metabolic processes, especially in glycolysis. Gene knockout models in mice have been instrumental in revealing its role in various biological processes and disease conditions. In cardiac repair, platelet production, and trophoblast function, LDHA plays significant roles, providing potential therapeutic targets for related diseases.