Ppm1k-flox Mouse

Ppm1k, also named as PP2Cm or branched-chain α -ketoacid dehydrogenase complex phosphatase, is a member of the metal-dependent phosphatase family. It is predominantly located in the mitochondrial matrix and plays a crucial role in the metabolism of branched-chain amino acids (BCAAs). Ppm1k is associated with various cellular functions and is related to diseases such as Alzheimer's, cardiomyopathy, and maple syrup urine disease (MSUD) [3,4].

Ppm1k-deficient female mice had increased BCAA levels and exhibited PCOS-like traits, including hyperandrogenemia and abnormal follicle development. A reduction in dietary BCAA intake significantly improved the endocrine and ovarian dysfunction of Ppm1k-/-female mice. In human granulosa cells, knockdown of PPM1K promoted the conversion of glycolysis to pentose phosphate pathway and inhibited mitochondrial oxidative phosphorylation, indicating that Ppm1k deficiency-impaired BCAA catabolism causes the occurrence and development of PCOS [1]. Also, in neurons, knockdown of PPM1K induced neuronal ferroptosis due to defective BCAA catabolism after cerebral ischemia-reperfusion injury [2].

In conclusion, Ppm1k is essential for the normal catabolism of BCAAs. The study of Ppm1k-deficient mouse models has revealed its significance in diseases like PCOS and cerebral ischemia-reperfusion injury, highlighting its potential as a therapeutic target in these disease areas.