Adss1-flox Mouse

Adss1, encoding adenylosuccinate synthetase 1, is a key component in adenine nucleotide biosynthesis. It is one of the enzymes in the purine nucleotide cycle, which is muscle-specific [3]. Adenylosuccinate synthetase (ADSS) catalyzes a key step in AMP synthesis, and Adss1 is one of its isozymes in vertebrates [1].

In rodent models, Adss1 is up-regulated in surgically induced cardiac hypertrophy [2]. In an in vitro hypertrophy system of rat neonatal cardiomyocytes treated with angiotensin II, a signaling cascade activates the Adss1 gene, and this induction is blocked by cyclosporin A, suggesting calcineurin's involvement. The induction requires an NFAT binding site upstream of the Adss1 transcription start site [2]. Additionally, in cultured cardiomyocytes, electrical stimulation activates the NFAT3 and GATA4 pathways, leading to Adss1 gene up-regulation [5]. Mutations in Adss1 can cause ADSS1 myopathy, an autosomal recessive muscle disease complicated by respiratory muscle weakness, cardiomyopathy, and limb muscle weakness [4].

In conclusion, Adss1 is crucial for adenine nucleotide biosynthesis, especially in muscle-related metabolic cycles. Research on rodent models and in vitro cell systems has revealed its role in cardiac hypertrophy and muscle-related diseases. Understanding Adss1's function through these models provides insights into the mechanisms of cardiac and muscle-associated disorders, which may contribute to the development of related treatments.