Nectin1-KO Mouse

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 is the primary receptor for several alpha-herpesviruses, such as herpes simplex virus (HSV), pseudorabies virus (PRV), and bovine herpesvirus 1 (BHV-1) [2]. It also plays a role in adherens junction formation, which is crucial for maintaining tissue integrity and cell-cell communication [3,5]. Genetic models, like KO mouse models, are valuable for studying its functions.

A nectin1-mutant mouse model with a single amino acid substitution (F129A) showed resistance to pseudorabies virus (PRV) infection. Homozygous mutant mice had alleviated disease manifestations, decreased death rate, and lower viral loading in serum and tissue compared to heterozygous mutant and wild-type mice. However, they also had a defect in eye development, indicating that single-amino-acid substitution in nectin1 can have side-effects on animal development [1]. In melanoma, loss of NECTIN1 triggers cell migration in vitro and tumor spreading in vivo, specifically in response to decreased IGF1 signaling. NECTIN1 loss was found in 55% of human melanoma cases, establishing it as a major determinant of melanoma dissemination [3]. In neonatally stressed male mice, decreased nectin1 levels in the medial entorhinal cortex (MEC) led to impaired spatial memory, suggesting that disruption of presynaptic nectin1-mediated interneuronal adhesion in the MEC-CA1 pathway contributes to early-life stress-induced memory deficits [4].

In summary, Nectin1 is essential for cell-cell adhesion, viral receptor functions, and plays a role in adherens junction formation. The study of Nectin1 using KO mouse models has provided insights into its role in diseases such as viral infections, melanoma, and early-life stress-related cognitive disorders. Understanding Nectin1 functions can potentially lead to new strategies for treating these diseases.

References:

1. Yang, Xiaohui, Yu, Chuanzhao, Zhang, Qiuyan, Wu, Zhenfang, Yang, Huaqiang. 2022. A Nectin1 Mutant Mouse Model Is Resistant to Pseudorabies Virus Infection. In Viruses, 14, . doi:10.3390/v14050874. https://pubmed.ncbi.nlm.nih.gov/35632616/

2. Qi, Shuhui, Sun, Chao, Wang, Jing, Jiang, Zhigang, Yin, Xin. 2024. Identification of NECTIN1 as a novel restriction factor for flavivirus infection. In mBio, 15, e0270824. doi:10.1128/mbio.02708-24. https://pubmed.ncbi.nlm.nih.gov/39570015/

3. Ablain, Julien, Al Mahi, Amira, Rothschild, Harriet, Lian, Christine G, Zon, Leonard I. 2022. Loss of NECTIN1 triggers melanoma dissemination upon local IGF1 depletion. In Nature genetics, 54, 1839-1852. doi:10.1038/s41588-022-01191-z. https://pubmed.ncbi.nlm.nih.gov/36229674/

4. Wu, Chen, Gong, Qian, Xu, Xue, Chen, Wei, Wang, Xiao-Dong. 2022. Disrupted presynaptic nectin1-based neuronal adhesion in the entorhinal-hippocampal circuit contributes to early-life stress-induced memory deficits. In Translational psychiatry, 12, 141. doi:10.1038/s41398-022-01908-y. https://pubmed.ncbi.nlm.nih.gov/35379771/

5. Takahashi, Yu, Yamamichi, Nobutake, Inada, Ken-Ichi, Tsutsumi, Yutaka, Koike, Kazuhiko. 2018. Nectin1 expression is frequently decreased in gastric cancers. In Pathology international, 68, 557-562. doi:10.1111/pin.12721. https://pubmed.ncbi.nlm.nih.gov/30221498/