Adamts14-KO Mouse

ADAMTS14, short for A disintegrin and metalloproteinase with thrombospondin motifs 14, is a member of the ADAMTS metalloproteinase family. It plays roles in extracellular matrix (ECM) assembly and degradation, and is involved in processes like pro-VEGFC activation. Through this activation, it is associated with lymphatic homeostasis [1].

In in vivo studies, genetic ablation of Adamts14 in adult mice showed no impact on skin lymphedema development, while Adamts2-deficient mice developed skin lymphedema due to lymphatic vessel changes [1]. In a corneal thermal cauterization model, lymphangiogenesis was reduced in Adamts14-KO mice, and further repressed in Adamts2/Adamts14 double-KO mice, indicating its role in lymphatic vasculature homeostasis in pathological processes [1]. In pancreatic cancer-related studies, loss of ADAMTS14 promoted myofibroblast differentiation and invasion, regulating this process through the TGF-β availability [2].

In conclusion, ADAMTS14 is crucial for pro-VEGFC activation and lymphatic vasculature homeostasis in adulthood. Gene-knockout mouse models have revealed its functions in lymphatic-related physiological and pathological processes, as well as in pancreatic cancer-associated myofibroblast activities. Understanding ADAMTS14 can potentially provide insights into the mechanisms of lymphatic-related diseases and pancreatic cancer progression.

References:

1. Dupont, Laura, Joannes, Loïc, Morfoisse, Florent, Noël, Agnès, Colige, Alain Cma. 2022. ADAMTS2 and ADAMTS14 can substitute for ADAMTS3 in adults for pro-VEGFC activation and lymphatic homeostasis. In JCI insight, 7, . doi:10.1172/jci.insight.151509. https://pubmed.ncbi.nlm.nih.gov/35316211/

2. Carter, Edward P, Yoneten, Kubra K, Gavara, Nuria, Pearce, Oliver, Grose, Richard P. 2023. Opposing roles for ADAMTS2 and ADAMTS14 in myofibroblast differentiation and function. In The Journal of pathology, 262, 90-104. doi:10.1002/path.6214. https://pubmed.ncbi.nlm.nih.gov/37929635/