Nectin1, also known as CD111 or PVRL1, is a cell adhesion molecule belonging to the immunoglobulin superfamily. It is involved in cell-cell adhesion and has been considered the primary receptor for several alpha herpesviruses [2]. It may also participate in various biological processes such as adherens junction formation and has potential implications in multiple pathways related to development and disease. Genetic models, especially knockout (KO) mouse models, are valuable for studying its functions.

A Nectin1-mutant mouse model with a single amino acid substitution (F129A) showed significantly alleviated disease manifestations, decreased death rate, and viral loading when infected with a highly virulent pseudorabies virus (PRV) strain, indicating that gene modification in Nectin1 can confer PRV resistance [1]. In melanoma, loss-of-function studies showed that NECTIN1 loss stimulates melanoma cell migration in vitro and spreading in vivo in response to decreased IGF1 signaling, establishing it as a major determinant of melanoma dissemination [3]. In neonatally stressed male mice, postnatal suppression or conditional inactivation of Nectin1 in the medial entorhinal cortex (MEC) impaired spatial memory and reproduced stress-induced deficits in MEC-dependent memories and neuronal plasticity in CA1, suggesting its role in stress-related cognitive disorders [4].

In conclusion, Nectin1 is crucial for cell-cell adhesion and plays diverse roles in virus-host interactions, cancer metastasis, and cognitive functions. Studies using KO or mutant mouse models have significantly contributed to understanding its role in diseases such as PRV-related infections, melanoma, and early-life stress-induced memory deficits.