Neuroimmunology Program, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomédiques August Pi i Sunyer-Caixa Research Institute (CRI), Universitat de Barcelona, Barcelona, Spain.
Alzheimer's Disease and Other Cognitive Disorders Unit, Neurology Service, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Front Immunol. 2024 Feb 2;15:1347948. doi: 10.3389/fimmu.2024.1347948. eCollection 2024.
Anti-IgLON5 disease is a neurological disorder characterized by autoantibodies against IgLON5 and pathological evidence of neurodegeneration. IgLON5 is a cell adhesion molecule of unknown function that is highly expressed in the brain. Our aim was to investigate the impact of IgLON5 loss-of-function in evaluating brain morphology, social behavior, and the development of symptoms observed in an IgLON5 knockout (IgLON5-KO) mouse model.
The IgLON5-KO mice were generated using CRISPR-Cas9 technology. Immunohistochemistry on fixed sagittal brain sections and Western blotting brain lysates were used to confirm IgLON5 silencing and to evaluate the presence of other cell surface proteins. Two- month-old IgLON5-KO and wild-type (WT) mice underwent a comprehensive battery of behavioral tests to assess 1) locomotion, 2) memory, 3) anxiety, 4) social interaction, and 5) depressive-like behavior. Brain sections were examined for the presence of anatomical abnormalities and deposits of hyperphosphorylated tau in young adult (2-month-old) and aged (22-month-old) mice.
Mice did not develop neurological symptoms reminiscent of those seen in patients with anti-IgLON5 disease. Behavioral testing revealed that 2-month-old IgLON5-KO mice showed subtle alterations in motor coordination and balance. IgLON5-KO females exhibited hyperactivity during night and day. Males were observed to have depressive-like behavior and excessive nest-building behavior. Neuropathological studies did not reveal brain morphological alterations or hyperphosphorylated tau deposits.
IgLON5-KO mice showed subtle alterations in behavior and deficits in fine motor coordination but did not develop the clinical phenotype of anti-IgLON5 disease.
抗 IgLON5 病是一种以针对 IgLON5 的自身抗体和神经退行性病变为特征的神经疾病。IgLON5 是一种功能未知的细胞黏附分子，在大脑中高度表达。我们的目的是研究 IgLON5 功能丧失对评估脑形态、社会行为以及 IgLON5 敲除 (IgLON5-KO) 小鼠模型中观察到的症状发展的影响。
使用 CRISPR-Cas9 技术生成 IgLON5-KO 小鼠。对固定矢状脑切片进行免疫组织化学染色和脑裂解物的 Western blot 分析，以确认 IgLON5 沉默，并评估其他细胞表面蛋白的存在。对 2 个月大的 IgLON5-KO 和野生型 (WT) 小鼠进行全面的行为测试，以评估 1) 运动，2) 记忆，3) 焦虑，4) 社交互动，5) 抑郁样行为。检查年轻成年 (2 个月大) 和老年 (22 个月大) 小鼠大脑切片中是否存在解剖异常和过度磷酸化 tau 沉积。
小鼠未出现类似于抗 IgLON5 病患者所见的神经症状。行为测试显示，2 个月大的 IgLON5-KO 小鼠在运动协调和平衡方面存在细微变化。IgLON5-KO 雌性小鼠在白天和黑夜都表现出过度活跃。雄性小鼠表现出抑郁样行为和过度筑巢行为。神经病理学研究未发现大脑形态改变或过度磷酸化 tau 沉积。
IgLON5-KO 小鼠在行为上存在细微改变，精细运动协调能力受损，但未出现抗 IgLON5 病的临床表型。
