Ass1-KO Mouse

ASS1, also known as argininosuccinate synthetase 1, is a key enzyme in the urea cycle and the citrulline - nitric oxide cycle. It converts citrulline into argininosuccinate. This enzyme's function is crucial for maintaining nitrogen balance and is involved in various biological processes related to metabolism and immune response [1,5].

In macrophages, IFN - γ and/or LPS stimulation promotes STAT1 - mediated ASS1 transcription and JAK2 - mediated phosphorylation of ASS1 at tyrosine 87, leading to citrulline depletion, which is required for efficient proinflammatory signaling activation. Blockage of ASS1 - mediated citrulline depletion suppresses the host defense against bacterial infection in vivo, highlighting its role in innate immune - signaling [1].

In non - small cell lung cancer cells, loss of ASS1 increases sensitivity to erastin - induced ferroptosis both in vitro and in vivo, as ASS1 promotes reductive carboxylation of cytosolic glutamine and confers ferroptosis resistance [2].

In ovarian cancer, disruption of the ASS1 - related AMP/ATP balance activates AMPK and CPT1A, enhancing fatty acid oxidation (FAO) and anoikis resistance [3].

In colon cancer cells, prolonged loss of ASS1 promotes DNA damage, and following DNA damage, ASS1 is part of the p53 network that pauses cell cycle progression [4].

In triple - negative breast cancer, ASS1 binds to PHGDH and promotes its degradation to inhibit serine synthesis and tumorigenesis [6].

In the liver, down - regulation of ASS1 in the TAA - induced liver injury model is rescued by activation of FXR, which promotes ASS1 transcription and alleviates liver injury [7].

In conclusion, ASS1 is essential in multiple biological processes. Its role in immune response, cancer cell survival, and liver injury has been revealed through in vivo studies including gene - knockout (KO) or conditional - knockout (CKO) mouse models in relevant disease areas such as bacterial infection, cancer, and acute liver injury. These findings contribute to understanding the mechanisms of disease occurrence and may provide new therapeutic targets.