Cordner Zachary A, Khambadkone Seva G, Zhu Shanshan, Bai Justin, Forti R Rasadokht, Goodman Ethan, Tamashiro Kellie L K, Ross Christopher A
Behavioral Neuroscience, Department of Psychiatry & Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Cellular & Molecular Medicine Graduate Program, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Complex Psychiatry. 2021 Dec;7(3-4):71-79. doi: 10.1159/000518819. Epub 2021 Aug 3.
The locus has been repeatedly found to confer an increased risk for bipolar disorder. codes for Ankyrin-G (Ank-G), a scaffold protein concentrated at axon initial segments, nodes of Ranvier, and dendritic spines, where it organizes voltage-gated sodium and potassium channels and cytoskeletal proteins. Mice with homozygous conditional knockout of Ank-G in the adult forebrain display hyperactivity and reduced anxiety-like behaviors, responsive to mood stabilizers. Their behavior switches to a depression-like phenotype when exposed to chronic social defeat stress (SDS), and then spontaneously reverts to baseline hyperactivity. Ank-G heterozygous conditional knockouts (Ank-G Het cKO) have not previously been characterized. Here, we describe the behavior of Ank-G Het cKO mice compared to littermate controls in the open field, elevated plus maze, and forced swim test, under both unstressed and stressed conditions. We found that Ank-G Het cKO is not significantly different from controls at baseline or after chronic SDS. The chronic stress-induced "depression-like" behavioral phenotype is persistent for at least 28 days and is responsive to fluoxetine. Strikingly, Ank-G Het cKO mice display increased sensitivity to a short duration SDS, which does not affect controls. The heterozygous Ank-G genetic model may provide novel insights into the role of Ank-G in the pathophysiology of stress sensitivity and "depression-like" phenotypes and could be useful for studying Ank-G-related gene-environment interactions.
该基因座已被反复发现会增加患双相情感障碍的风险。它编码锚蛋白G（Ank-G），一种集中在轴突起始段、郎飞结和树突棘的支架蛋白，在这些部位它组织电压门控钠通道和钾通道以及细胞骨架蛋白。成年前脑Ank-G纯合条件性敲除的小鼠表现出多动和焦虑样行为减少，对情绪稳定剂有反应。当暴露于慢性社会挫败应激（SDS）时，它们的行为转变为抑郁样表型，然后自发恢复到基线多动状态。此前尚未对Ank-G杂合条件性敲除（Ank-G Het cKO）小鼠进行特征描述。在这里，我们描述了在无应激和应激条件下，Ank-G Het cKO小鼠与同窝对照小鼠在旷场试验、高架十字迷宫试验和强迫游泳试验中的行为表现。我们发现，Ank-G Het cKO小鼠在基线时或慢性SDS后与对照小鼠没有显著差异。慢性应激诱导的“抑郁样”行为表型至少持续28天，并且对氟西汀有反应。引人注目的是，Ank-G Het cKO小鼠对短时间的SDS表现出更高的敏感性，而这对对照小鼠没有影响。Ank-G杂合基因模型可能为Ank-G在应激敏感性和“抑郁样”表型的病理生理学中的作用提供新的见解，并且可能有助于研究Ank-G相关的基因-环境相互作用。
