Mice lacking full length Adgrb1 (Bai1) exhibit social deficits, increased seizure susceptibility, and altered brain development

• Type of Material: Article
• Authors: Fu Hung Shiu, Emory University; Jennifer Wong, Emory University; Takahiro Yamamoto, Univ Alabama Birmingham UAB; Trisha Lala, Emory University; Ryan Purcell, Emory University; Sharon Owino, Emory University; Dan Zhu, Emory University; Erwin Van Meir, Emory University; Randy Hall, Emory University; Andrew Escayg, Emory University
• Language: English
• Date: 2022-02-16
• Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.expneurol.2022.113994
• Title of Journal or Parent Work: EXPERIMENTAL NEUROLOGY
• Volume: 351
• Start Page: 113994
• End Page: 113994
• Grant/Funding Information: This work was supported by the National Institutes of Health (EGVM, CA096236 and NS117666), Emory University Integrated Cellular Imaging Microscopy Core of the Emory Neuroscience NINDS Core Facilities grant (5P30NS055077), and by an Emory Brain Health Center seed grant (EGVM, RAH, AE). The content is solely the responsibility of the authors and does not necessarily reflect the official views of the National Institutes of Health.
• Keywords: APOPTOTIC CELLS; MOUSE; PROTEIN FAMILY; AUTISM SPECTRUM DISORDER; LONG-TERM POTENTIATION; Neurosciences; Science & Technology; Epilepsy; BAI1; Autism; MUNC13 PROTEIN; RECEPTOR; ANGIOGENESIS; GPCR; Life Sciences & Biomedicine; Seizures; Neurosciences & Neurology; EMERGING ROLES; EPILEPSY

Abstract

The adhesion G protein-coupled receptor BAI1/ADGRB1 plays an important role in suppressing angiogenesis, mediating phagocytosis, and acting as a brain tumor suppressor. BAI1 is also a critical regulator of dendritic spine and excitatory synapse development and interacts with several autism-relevant proteins. However, little is known about the relationship between altered BAI1 function and clinically relevant phenotypes. Therefore, we studied the effect of reduced expression of full length Bai1 on behavior, seizure susceptibility, and brain morphology in Adgrb1 mutant mice. We compared homozygous (Adgrb1−/−), heterozygous (Adgrb1+/−), and wild-type (WT) littermates using a battery of tests to assess social behavior, anxiety, repetitive behavior, locomotor function, and seizure susceptibility. We found that Adgrb1−/− mice showed significant social behavior deficits and increased vulnerability to seizures. Adgrb1−/− mice also showed delayed growth and reduced brain weight. Furthermore, reduced neuron density and increased apoptosis during brain development were observed in the hippocampus of Adgrb1−/− mice, while levels of astrogliosis and microgliosis were comparable to WT littermates. These results show that reduced levels of full length Bai1 is associated with a broader range of clinically relevant phenotypes than previously reported.