Mice lacking full length Adgrb1 (Bai1) exhibit social deficits, increased seizure susceptibility, and altered brain development.
Mice lacking full length Adgrb1 (Bai1) exhibit social deficits, increased seizure susceptibility, and altered brain development.
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DOI：
10.1016/j.expneurol.2022.113994
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发表时间：
2022-05
影响因子：
5.3
通讯作者：
Escayg, Andrew
中科院分区：
文献类型：
--
作者：
Shiu, Fu Hung;Wong, Jennifer C.;Yamamoto, Takahiro;Lala, Trisha;Purcell, Ryan H.;Owino, Sharon;Zhu, Dan;Van Meir, Erwin G.;Hall, Randy A.;Escayg, Andrew
粘附G蛋白偶联受体BAI1/ADGRB1在抑制血管生成、介导吞噬作用和充当脑肿瘤抑制剂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，并与多种自闭症相关蛋白相互作用。然而，人们对 BAI1 功能改变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 突变小鼠的行为、癫痫易感性和大脑形态的影响。我们使用一系列测试来比较纯合子 (Adgrb1−/−)、杂合子 (Adgrb1+/-) 和野生型 (WT) 同窝小鼠，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−/− 小鼠表现出显着的社交行为缺陷，并且更容易癫痫发作。 Adgrb1−/− 小鼠还表现出生长延迟和脑重量减轻。此外，在 Adgrb1−/− 小鼠的海马体中观察到大脑发育过程中神经元密度降低和细胞凋亡增加，而星形胶质细胞增生和小胶质细胞增生的水平与 WT 同窝小鼠相当。这些结果表明，全长 Bai1 水平的降低与比之前报道的更广泛的临床相关表型相关。
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.
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影响因子：
5.3
作者：
Dutton SBB;Dutt K;Papale LA;Helmers S;Goldin AL;Escayg A
通讯作者：
Escayg A
影响因子：
10.6
作者：
Amiet, Claire;Gourfinkel-An, Isabelle;Cohen, David
通讯作者：
Cohen, David
影响因子：
2.5
作者：
Ahern, Todd H.;Krug, Stefanie;Forger, Nancy G.
通讯作者：
Forger, Nancy G.
DOI：
10.1083/jcb.201004096
发表时间：
2010-06-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
Elliott MR;Ravichandran KS
通讯作者：
Ravichandran KS
影响因子：
3.1
作者：
Duman JG;Tu YK;Tolias KF
通讯作者：
Tolias KF