Nos1, also known as neuronal nitric oxide synthase (nNOS), is an enzyme that uses L-arginine as a substrate to produce nitric oxide (NO) in the tissue microenvironment. NO generated by Nos1 is involved in multiple functions, including learning, memory, synaptic plasticity, and neuronal development. It is highly enriched in the brain and is part of the nitric oxide signaling pathway, which is crucial for various physiological processes [1].

In mice, Nos1 deficiency leads to dose-dependent defects in sexual maturation, olfaction, hearing, and cognition. Five heterozygous NOS1 loss-of-function mutations were identified in six probands with congenital hypogonadotropic hypogonadism, who also showed anosmia, hearing loss, and intellectual disability [2]. Additionally, in melanoma cells, NOS1 deletion suppressed cell proliferation, blocked cell cycling, and decreased tumor growth in a xenograft mouse model. It also increased the infiltration of CD3 + immune cells in tumors [3]. In colon cancer cells, overexpression of NOS1 inhibited both basal and cisplatin-induced mitochondrial superoxide and cisplatin-induced apoptosis [4].

In conclusion, Nos1 plays essential roles in multiple biological processes. Mouse models with Nos1 deficiency or overexpression have revealed its significance in sexual maturation, sensory and cognitive functions, as well as in cancer-related processes such as tumor growth, apoptosis, and immune cell infiltration. These findings contribute to understanding the mechanisms underlying related diseases and potentially developing new therapeutic strategies.