Has1-flox Mouse

Has1, short for Hyaluronan synthase 1, is one of the three hyaluronan synthase isoenzymes in mammals. It synthesizes hyaluronan (HA), a crucial component of the extracellular matrix (ECM) and perineuronal nets (PNNs), providing binding sites for proteoglycans and other ECM components [1,3,5,6]. In addition to its role in ECM formation, Has1 is also involved in ribosome biogenesis in Saccharomyces cerevisiae [2].

In Alzheimer's disease (AD), the transcripts of Has1 were found to be reduced in AD patients and AβPP/PS1 mice. Phosphorylated tau (p-tau) mediates AβPP-induced cytosolic-nuclear translocation of Has1, negatively regulating its stability, monoubiquitination, and oligomerization, thus reducing HA synthesis and release [1]. In bladder cancer, Has1 transcript levels are elevated 5-to 10-fold in cancer tissues compared to normal tissues, and increased Has1 expression correlates with increased tissue HA levels and a positive HA urine test, potentially having prognostic value [3]. In non-small cell lung cancer, miR-125a inhibits the proliferation, invasion, and metastasis of cancer cells by reducing Has1 expression through targeting STAT3 [4].

In conclusion, Has1 is essential for the synthesis of hyaluronan, playing significant roles in various physiological and pathological processes. Studies in AD, bladder cancer, and non-small cell lung cancer models have revealed its functions in disease-related microenvironment remodeling, gene transcription, and cancer progression. Understanding the role of Has1 in these disease models may provide new insights into disease mechanisms and potential therapeutic targets.