What is it about?
The immunoglobulin superfamily (IgSF) of proteins is defined by the presence of structural domains consisting of roughly 130 amino acids forming the immunoglobulin ß-barrel fold that is stabilized by a disulfide bridge. These compact Ig-domains are ideally suited to act as adhesion molecules modulating interactions between proteins and cells. In male mice, lack of the Brain- and Testis-specific Ig superfamily protein (BT-IgSF, also termed IgSF11 and VSIG-3) results in infertility, most likely caused by a functionally impaired blood-testis barrier. In the nervous system, BT-IgSF regulates the stability of AMPA receptors in the membrane of neurons, modulates the connectivity of chandelier cells, and controls gap junction-mediated astrocyte-astrocyte communication. Therefore, BT-IgSF may modify the information flow in neuronal or astrocyte networks and affect behavior. In this study, we subjected BT-IgSF-deficient mice to behavioral tests and show that lack of BT-IgSF results in reduced anxiety or increased fear of darkness, reduced behavioral flexibility, and increased male aggression.
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Why is it important?
The identity of a species is determined by its genome. The mammalian genome encodes appr. 25.000 different genes. The functions are well understood only for a fraction of these genes and knowledge on their detailed role is still missing for many genes. Our study addresses for the first time whether BT-IgSF expression in the brain may modify information flow and as a consequence affect behavior. Our results show that specific behaviors are modified by the lack of BT-IgSF leading to distinct changes in open maze behavior, spatial orientation, and increased male aggression. Overall, we conclude that BT-IgSF expression in neurons and astrocytes may interfere with information flow in neuronal or astrocyte networks and as a consequence might modulate the network properties influencing behavioral performance. These results may be translated to the role of BT-IgSF in humans and indicate that variants of the BT-IgSF gene may impact male fertility and behavior affecting social interactions.
Perspectives
Elucidating the functions of genes is fundamental to understanding our genetic inheritance which defines our biological potential and limitations. This knowledge has great impact on medical diagnosis and intervention, psychological conditions, and treatment of diseases. The first approach of inactivating a gene and inferring its role from the loss of functions is a first step to characterize the genome. However, genetic interactions and complex regulatory networks are addressed by other technologies. The final synthesis of these investigations will potentially lead to an in-depth-understanding of the genome and its miraculous generation of new and exciting life.
Dirk Montag
Leibniz Institute for Neurobiology
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This page is a summary of: Lack of the Ig cell adhesion molecule BT-IgSF (IgSF11) induced behavioral changes in the open maze, water maze and resident intruder test, PLoS ONE, January 2023, PLOS,
DOI: 10.1371/journal.pone.0280133.
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