Parp6-flox Mouse

Parp6, a member of the poly-ADP-ribose polymerase (PARP) family, is a neuronally enriched mono-ADP-ribosyltransferase. It is involved in various biological processes such as regulating dendrite morphogenesis, cell cycle control, and is associated with pathways like the Wnt/β-catenin pathway [1,4,5,6]. Genetic models, especially knockout mouse models, are valuable tools to study its functions in vivo.

In knockout mouse models, homozygous Parp6 truncated variant (Parp6TR) mice, lacking catalytic activity, die perinatally, suggesting that Parp6 catalytic activity is crucial for postnatal survival [1]. In humans, PARP6 mutations are found in patients with neurodevelopmental disorders, and the most severe mutation (C563R) leads to loss of catalytic activity and decreased dendrite morphogenesis in hippocampal neurons [1].

In cancer research, in gastric cancer, PARP6 promotes cell proliferation, migration, and invasion by positively regulating Survivin [2]. However, in hepatocellular carcinoma, PARP6 suppresses proliferation and metastasis by degrading XRCC6 to regulate the Wnt/β-catenin pathway [3]. In colorectal cancer, it acts as a tumor suppressor by down-regulating Survivin expression [5]. Pharmacological inhibition of PARP6 in breast cancer triggers multipolar spindle formation and has antitumor effects, and Chk1 is identified as a substrate of PARP6 [7].

In conclusion, Parp6 is an essential microtubule-regulatory gene, especially important in neuronal function and postnatal survival in mice. In disease conditions, particularly in cancer, its role can be either tumor-promoting or tumor-suppressive depending on the cancer type. The study of Parp6 knockout mouse models has significantly contributed to understanding its functions in neurodevelopmental disorders and cancer.