Cntn5, also known as Contactin-5 or NB-2, is a neural cell adhesion molecule. It is involved in synaptogenesis, synaptic maturation in the auditory pathway, and plays a role in circuit formation and connectivity during early development as well as synaptic maintenance in adulthood [2]. It has been associated with pathways related to neurodevelopment.

Genetic studies have linked Cntn5 to neurodevelopmental disorders. In human iPSC-derived neurons from individuals with autism, CNTN5 -/+ neurons develop hyperactive neuronal networks, suggesting its role in autism-related neural network dysregulation [1]. In Cntn5 knockout mice, unexpected phenotypes were observed, including being leaner with elevated cardiovascular parameters, linking Cntn5 deficiency to obesity and hypertension [4]. Also, Cntn5 -/- mice showed thinning of the primary somatosensory cortex and a reduced barrel/septa ratio in the S1 barrel field, indicating its role in cerebral cortex development [3].

In summary, Cntn5 is crucial for neural development, especially in processes like synaptogenesis and circuit formation. The gene knockout mouse models have revealed its potential contributions to neurodevelopmental disorders such as autism, as well as to phenotypes related to obesity and hypertension. These findings highlight the importance of Cntn5 in understanding the mechanisms underlying these conditions.

References:

1. Deneault, Eric, Faheem, Muhammad, White, Sean H, Ellis, James, Scherer, Stephen W. 2019. CNTN5-/+or EHMT2-/+human iPSC-derived neurons from individuals with autism develop hyperactive neuronal networks. In eLife, 8, . doi:10.7554/eLife.40092. https://pubmed.ncbi.nlm.nih.gov/30747104/

2. Kleijer, K T E, Zuko, A, Shimoda, Y, Watanabe, K, Burbach, J P H. 2015. Contactin-5 expression during development and wiring of the thalamocortical system. In Neuroscience, 310, 106-13. doi:10.1016/j.neuroscience.2015.09.039. https://pubmed.ncbi.nlm.nih.gov/26391921/

3. Kleijer, Kristel T E, van Nieuwenhuize, Denise, Spierenburg, Henk A, Kas, Martien J H, Burbach, J Peter H. 2017. Structural abnormalities in the primary somatosensory cortex and a normal behavioral profile in Contactin-5 deficient mice. In Cell adhesion & migration, 12, 5-18. doi:10.1080/19336918.2017.1288788. https://pubmed.ncbi.nlm.nih.gov/28346043/

4. Smirnov, Alexander V, Kontsevaya, Galina V, Feofanova, Natalia A, Moshkin, Mikhail P, Serov, Oleg L. 2017. Unexpected phenotypic effects of a transgene integration causing a knockout of the endogenous Contactin-5 gene in mice. In Transgenic research, 27, 1-13. doi:10.1007/s11248-017-0053-y. https://pubmed.ncbi.nlm.nih.gov/29264679/