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

Biochem Biophys Res Commun. 2021 Apr 30:551:54-62. doi: 10.1016/j.bbrc.2021.03.015. Epub 2021 Mar 12.

Abstract

Octodon degus is said to be one of the most human-like rodents because of its improved cognitive function. Focusing on its high 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. According to our results, 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, whereas mouse Neuroligin4 is known to be poorly similar to human Neuroligin4X. Furthermore, our work also indicated that testosterone directly binds to degus Neurexin and intercepts intercellular Neurexin-Neuroligin binding. 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.

Keywords: Autism spectrum disorder; Neurexin; Neuroligin; Octodon degus; Testosterone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autism Spectrum Disorder / genetics
  • Autism Spectrum Disorder / metabolism
  • Calcium-Binding Proteins / chemistry
  • Cell Adhesion Molecules, Neuronal / chemistry
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Hippocampus / metabolism
  • Humans
  • Male
  • Neural Cell Adhesion Molecules / chemistry
  • Octodon / metabolism*
  • Protein Binding / drug effects
  • Protein Domains
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / metabolism*
  • Sex Hormone-Binding Globulin / chemistry
  • Testosterone / metabolism*
  • Testosterone / pharmacology

Substances

  • Calcium-Binding Proteins
  • Cell Adhesion Molecules, Neuronal
  • NLGN4X protein, human
  • NRXN1 protein, human
  • Neural Cell Adhesion Molecules
  • Receptors, Cell Surface
  • Sex Hormone-Binding Globulin
  • Testosterone