Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA; Neuroscience Graduate Program, Graduate Division of Biological and Biomedical Sciences, Laney Graduate School, Emory University, Atlanta, GA, USA.
Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA.
Exp Neurol. 2022 May;351:113994. doi: 10.1016/j.expneurol.2022.113994. Epub 2022 Jan 31.
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.
黏附 G 蛋白偶联受体 BAI1/ADGRB1 在抑制血管生成、介导吞噬作用和作为脑肿瘤抑制因子方面发挥着重要作用。BAI1 也是树突棘和兴奋性突触发育的关键调节因子，与几种自闭症相关蛋白相互作用。然而，关于改变的 BAI1 功能与临床相关表型之间的关系知之甚少。因此，我们研究了全长 Bai1 表达减少对 Adgrb1 突变小鼠行为、癫痫易感性和脑形态的影响。我们使用一系列测试比较了纯合子（Adgrb1）、杂合子（Adgrb1）和野生型（WT）同窝仔鼠，以评估社交行为、焦虑、重复行为、运动功能和癫痫易感性。我们发现 Adgrb1 小鼠表现出明显的社交行为缺陷和癫痫易感性增加。Adgrb1 小鼠的生长也延迟，脑重减轻。此外，在 Adgrb1 小鼠的海马体中观察到神经元密度降低和发育过程中细胞凋亡增加，而星形胶质细胞和小胶质细胞的水平与 WT 同窝仔鼠相当。这些结果表明，全长 Bai1 水平降低与比以前报道的更广泛的临床相关表型相关。
