Ppm1d-flox Mouse

PPM1D, also known as wild-type p53-induced phosphatase 1 (Wip1) or protein phosphatase 2C delta (PP2Cδ), encodes a serine/threonine phosphatase. It negatively regulates crucial cancer suppressor pathways, especially acting as a negative regulator of the tumour suppressor p53 within the DNA damage response pathway [3,4].

Using conditional mouse models, researchers found that Ppm1d regulates the competitive fitness and self-renewal of hematopoietic stem cells (HSCs) with and without exogenous genotoxic stresses. Loss of Ppm1d sensitizes leukemias to cytotoxic therapies in vitro and in vivo, even without a Ppm1d mutation [2]. In addition, heterozygous mutant Ppm1d hematopoietic cells outcompeted their wild-type counterparts in vivo after exposure to cisplatin and doxorubicin [1].

In conclusion, PPM1D plays a significant role in regulating hematopoietic cell fitness and response to DNA damage. The study of Ppm1d using KO/CKO mouse models has provided insights into its function in myeloid malignancy and clonal hematopoiesis, suggesting that targeting PPM1D could be a potential therapeutic strategy for related diseases [1,2].