Asl, short for argininosuccinate lyase, is an enzyme-encoding gene. The Asl-encoded argininosuccinate lyase is a key enzyme in the urea cycle, which cleaves argininosuccinic acid to arginine and fumarate. Deficiency in Asl leads to argininosuccinic aciduria (ASA), causing hepatocyte dysfunction, hyperammonemia, encephalopathy, and respiratory alkalosis [1,2].

In LC-Asl-conditional knockout (CKO) mice, depletion of Asl in locus coeruleus (LC) neurons leads to reduced amount and activity of tyrosine hydroxylase (TH), decreased catecholamines synthesis due to decreased nitric oxide (NO) signaling. These mice also show increased seizure reactivity and altered response to stressful stimuli. NO donors can normalize catecholamine levels, seizure sensitivity, and stress response in these mice, emphasizing the importance of Asl for the metabolic regulation of LC function, which is relevant for Asl deficiency (ASLD) patients [3].

In conclusion, Asl is crucial for the urea cycle and has a significant impact on metabolic regulation in the locus coeruleus. The use of LC-Asl-CKO mouse models has revealed its role in specific biological processes and provided insights into the pathophysiology of ASL-deficiency-related diseases, offering potential directions for understanding and treating such conditions.