Testosterone interrupts binding of Neurexin and Neuroligin that are expressed in a highly socialized rodent, Octodon degus.

Abstract Octodon degus is said to be one of the most human-like rodents because of its improved cognitive function. Notably, it has a complicated vocal communication system. Focusing on its highly developed sociality, we cloned and characterized some sociality-related genes of degus, in order to establish degus as a highly socialized animal model in molecular biology. We cloned degus Neurexin and Neuroligin as sociality-related genes, which are genetically related to autism spectrum disorder in human. They bind to each other at synaptic cleft, and this intercellular binding is also important for regulation of social behavior. Interestingly, amino acid sequences of Neurexin and Neuroligin expressed in degus brain, are highly conserved to that of human sequences. Most notably, degus Neuroligin4 is highly similar to human Neuroligin4X, which is one of the most important autism-related genes. Mouse neuroligin4 is known to be poorly similar to human Neuroligin4X, leading to the difficulty of Neuroligin4X investigation. Furthermore, our work also indicated that testosterone directly binds to degus Neurexin and intercepts intercellular Neurexin-Neuroligin binding. This effect of testosterone is unique in that it directly affects to protein function without hormone receptor signaling. Moreover, it is of high interest that testosterone is another key molecule of the higher incidence of autism in male. These results indicated that degus has the potential for animal model of sociality, and furthermore may promote understanding toward the pathogenic mechanism of autism.