Mark2-flox Mouse

MARK2, also known as Microtubule-Affinity Regulating Kinase 2, is a serine/threonine protein kinase. It phosphorylates microtubule-associated proteins and is involved in multiple signaling pathways such as WNT, PI3K/AKT/mTOR, and NF-κB, playing crucial roles in cancer and the nervous system [3].

In the nervous system, MARK2 contributes to establishing neuronal polarity, developing dendritic spines, and regulating polarized vesicular transport. Mark2+/- mice showed abnormal cortical formation and partition and ASD-like behavior, suggesting MARK2 loss leads to early neuronal developmental and functional deficits via down-regulation of the WNT/β-catenin signaling pathway, thus linking it to autism spectrum disorder (ASD) [1].

In cancer, MARK2 has been studied in various contexts. For example, it is a catalytic codependency of YAP/TAZ in human cancer, and its inhibition can re-activate the Hippo tumor-suppressive pathway [2]. It also regulates chemotherapeutic responses in pancreatic cancer through the class IIa HDAC-YAP axis [4], and promotes aerobic glycolysis-mediated cell growth in breast cancer by regulating mTOR/HIF-1α and p53 pathways [5].

In conclusion, MARK2 is essential for normal neuronal development and is intricately involved in cancer-related processes. Studies using Mark2+/- mouse models have been instrumental in revealing its role in ASD, while in-vitro and in-vivo studies in cancer models have demonstrated its significance in cancer cell growth, metastasis, and chemosensitivity. This understanding of MARK2 provides potential therapeutic targets for treating ASD and certain cancers.