Generation and initial characterization of mice lacking full‐length BAI3 (ADGRB3) expression

Abstract

Brain‐specific angiogenesis inhibitor 3 (ADGRB3/BAI3) belongs to the family of adhesion G protein‐coupled receptors. It is most highly expressed in the brain where it plays a role in synaptogenesis and synapse maintenance. Genome‐wide association studies have implicated ADGRB3 in disorders such as schizophrenia and epilepsy. Somatic mutations in ADGRB3 have also been identified in cancer. To better understand the in vivo physiological role of ADGRB3, we used CRISPR/Cas9 editing to generate a mouse line with a 7‐base pair deletion in Adgrb3 exon 10. Western blot analysis confirmed that homozygous mutants (Adgrb3∆7/∆7) lack full‐length ADGRB3 expression. The mutant mice were viable and reproduced in Mendelian ratios but demonstrated reduced brain and body weights and deficits in social interaction. Measurements of locomotor function, olfaction, anxiety levels and prepulse inhibition were comparable between heterozygous and homozygous mutants and wild‐type littermates. Since ADGRB3 is also expressed in organs such as lung and pancreas, this new mouse model will facilitate elucidation of ADGRB3's role in non‐central nervous system‐related functions. Finally, since somatic mutations in ADGRB3 were identified in patients with several cancer types, these mice can be used to determine whether loss of ADGRB3 function contributes to tumour development.

Welcome to Basic & Clinical Pharmacology & Toxicology 2024

“…As we embark on the new year, we invite you to explore the wealth of knowledge and exciting content our journal offers. In 2023, we published three Special Collections from focused conferences supported by the Nordic Association for the Publication of Basic and Clinical Pharmacology and Toxicology, including Adhesion G‐Protein‐coupled Receptors, 1–10 Transmembrane Transporter Proteins: Catching Transport in Motion 11–19 and Advancing Deprescribing: Learnings from the first International Conference on Deprescribing 20–31 . The second part of the latter Special Collection will appear in the January 2024 issue.…”