Nova1, also known as Neuro-oncological ventral antigen 1, is a neuron-specific RNA-binding protein. It functions as a brain-specific splicing factor, regulating neuronal alternative splicing. It is involved in multiple biological processes, including neural development, metabolism, and is associated with various pathways such as Wnt/β-catenin signaling. Its study is facilitated by genetic models like gene knockout and conditional knockout mouse models, which help in understanding its in-vivo functions [2,3,4,5].

In disease-related research, in glioblastoma cells, Nova1 acts as an oncogenic factor, antagonizing AGO2-miRNA actions to up-regulate cholesterol synthesis and promote cell viability [1]. In non-small cell lung cancer (NSCLC), high Nova1 expression promotes cell proliferation and invasion via activating Wnt/β-catenin signaling, and may serve as a potential prognosis biomarker [2]. In a patient haploinsufficient for Nova1, a behavioral motor hyperactivity disorder was observed, and in conditional Nova1-null mice (Nova1-cKOGad2-cre), phenotypes similar to the patient were found, with Nova1 affecting hypothalamic function by stabilizing Impact mRNA [3]. In retinoblastoma, miR-338-3p acts as a tumor suppressor by targeting Nova1 [6]. In spinal muscular atrophy, Nova1 promotes SMN2 exon 7 splicing, increasing SMN protein expression [7].

In conclusion, Nova1 plays essential roles in neural development, metabolism, and is involved in various diseases including cancers and neurological disorders. The use of KO/CKO mouse models has been crucial in revealing its functions in these specific biological processes and disease conditions, providing insights into the underlying molecular mechanisms and potential therapeutic targets.