Usp11-flox Mouse

Usp11, a member of the ubiquitin-specific protease family, is a deubiquitinating enzyme. It is involved in regulating multiple biological processes such as the cell cycle, DNA repair, and various signaling pathways. By deubiquitinating target proteins, Usp11 can affect their stability, function, and subsequent cellular responses, which is of great biological importance [6].

In spinal cord ischemia-reperfusion injury, knockout of Usp11 (Usp11-/Y) significantly decreased neuronal cell ferroptosis and promoted functional recovery in mice, suggesting Usp11 promotes autophagy-dependent ferroptosis in this context [1]. In intervertebral disc degeneration, knockout of Usp11 in vivo (Usp11-/-) resulted in exacerbated disease and poor pain-related behavioral scores, while its overexpression ameliorated oxidative stress-induced ferroptosis by stabilizing Sirt3 [2]. In hepatocellular carcinoma, knockdown of Usp11 inhibited its metastasis-promoting effect via the eEF1A1/SP1/HGF-dependent EMT pathway [3]. In radiation-induced pneumonitis, Usp11-/-mice showed alleviated disease progression with reduced pro-inflammatory cytokine expression, decreased pulmonary vessel permeability, and less immune cell infiltration [4]. In colorectal cancer, depletion of Usp11 increased cell sensitivity to ferroptosis, as it stabilizes LSH through deubiquitination to inhibit ferroptosis [5]. In prostate cancer, Usp11 knockdown significantly inhibited cell growth, and it promotes cancer progression by up-regulating AR and c-Myc activities [7].

In conclusion, Usp11 plays diverse and crucial roles in multiple biological processes and disease conditions. Gene knockout mouse models have been instrumental in revealing its functions, such as in ferroptosis-related diseases like spinal cord ischemia-reperfusion injury, intervertebral disc degeneration, and colorectal cancer, as well as in cancer metastasis and progression in hepatocellular carcinoma and prostate cancer. Understanding Usp11's functions through these models provides potential therapeutic targets for these diseases.