PDF(Pubmed)
Abstract：
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.
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.
摘要：
■抗IgLON5疾病是一种神经系统疾病，其特征是针对IgLON5的自身抗体和神经变性的病理证据。IgLON5是一种功能未知的细胞粘附分子，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的影响，社会行为,和在IgLON5敲除(IgLON5-KO)小鼠模型中观察到的症状的发展。
使用CRISPR-Cas9技术产生IgLON5-KO小鼠。在固定的矢状脑切片上的免疫组织化学和蛋白质印迹脑裂解物用于确认IgLON5沉默并评估其他细胞表面蛋白的存在。两个月大的IgLON5-KO和野生型（WT）小鼠进行了一系列全面的行为测试，以评估1）运动，2）记忆，3）焦虑，4）社会交往，5)类似抑郁的行为。在年轻成年（2个月大）和老年（22个月大）小鼠中检查脑切片的解剖异常和过度磷酸化tau沉积的存在。
小鼠没有出现神经症状，这让人联想到在抗IgLON5病患者中看到的症状。行为测试表明，2个月大的IgLON5-KO小鼠在运动协调和平衡方面表现出细微的变化。IgLON5-KO女性在夜间和白天表现出多动症。观察到雄性具有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的tau沉积物。
■IgLON5-KO小鼠表现出细微的行为改变和精细运动协调缺陷，但没有发展出抗IgLON5疾病的临床表型。
使用CRISPR-Cas9技术产生IgLON5-KO小鼠。在固定的矢状脑切片上的免疫组织化学和蛋白质印迹脑裂解物用于确认IgLON5沉默并评估其他细胞表面蛋白的存在。两个月大的IgLON5-KO和野生型（WT）小鼠进行了一系列全面的行为测试，以评估1）运动，2）记忆，3）焦虑，4）社会交往，5)类似抑郁的行为。在年轻成年（2个月大）和老年（22个月大）小鼠中检查脑切片的解剖异常和过度磷酸化tau沉积的存在。
小鼠没有出现神经症状，这让人联想到在抗IgLON5病患者中看到的症状。行为测试表明，2个月大的IgLON5-KO小鼠在运动协调和平衡方面表现出细微的变化。IgLON5-KO女性在夜间和白天表现出多动症。观察到雄性具有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的tau沉积物。
■IgLON5-KO小鼠表现出细微的行为改变和精细运动协调缺陷，但没有发展出抗IgLON5疾病的临床表型。
