Fstl1-flox Mouse

Fstl1, also known as follistatin-related protein 1, is a secreted glycoprotein involved in multiple physiological functions [2]. It has been associated with various signaling cascades such as TGF-β/BMP/Smad, AKT, NF-κB, and Wnt-β-catenin signaling pathways [2]. Genetic models, especially gene knockout mouse models, have been crucial in understanding its functions.

In liver fibrosis, myeloid-specific Fstl1-knockout (Fstl1M-KO) mice demonstrated that macrophage Fstl1 promotes liver fibrosis progression. Fstl1 deficiency attenuated liver fibrosis, reduced inflammation, suppressed M1 macrophage polarization and NF-κB pathway activation. Fstl1 bound to PKM2, promoted its phosphorylation and nuclear translocation, enhanced PKM2-dependent glycolysis and M1 polarization [1].

In non-alcoholic steatohepatitis (NASH), skeletal muscle specific IRF4 knockout (F4MKO) mice showed ameliorated hepatic steatosis, inflammation, and fibrosis. Proteomics analysis suggested Fstl1 as a link between muscles and the liver, and its induction in F4MKO muscles restored liver pathology [3].

In osteosarcoma, Fstl1 knockout in OS cells suppressed cellular functions, and the ablated tumor cells were rejected due to potent NK cell generation. Blocking Fstl1 restored NK activity and suppressed tumor growth and metastasis in mouse OS models [4].

In conclusion, Fstl1 plays diverse and significant roles in multiple biological processes and disease conditions. Gene knockout mouse models have been instrumental in revealing its functions in liver fibrosis, NASH, and osteosarcoma, among others, highlighting its potential as a therapeutic target for these diseases.