TY - JOUR
T1 - Phenotypic Insights Into Anti-IgLON5 Disease in IgLON5-Deficient Mice
AU - Lee, Sin Yi
AU - Shoji, Hirotaka
AU - Shimozawa, Aki
AU - Aoyagi, Hirofumi
AU - Sato, Yoshiaki
AU - Tsumagari, Kazuya
AU - Terumitsu, Mika
AU - Motegi, Haruhiko
AU - Okada, Kensuke
AU - Sekiguchi, Koji
AU - Kuromitsu, Junro
AU - Nakahara, Jin
AU - Miyakawa, Tsuyoshi
AU - Ito, Daisuke
N1 - Publisher Copyright:
© 2024 The Author(s).
PY - 2024/4/24
Y1 - 2024/4/24
N2 - Background and Objectives Anti-IgLON5 disease is an autoimmune neurodegenerative disorder characterized by various phenotypes, notably sleep and movement disorders and tau pathology. Although the disease is known to be associated with the neuronal cell adhesion protein IgLON5, the physiologic function of IgLON5 remains elusive. There are conflicting views on whether autoantibodies cause loss of function, activation of IgLON5, or inflammation-associated neuronal damage, ultimately leading to the disease. We generated IgLON5 knockout (−/−) mice to investigate the functions of IgLON5 and elucidate the pathomechanism of anti-IgLON5 disease. Methods IgLON5 knockout (−/−) mice underwent behavioral tests investigating motor function, psychiatric function (notably anxiety and depression), social and exploratory behaviors, spatial learning and memory, and sensory perception. Histologic analysis was conducted to investigate tau aggregation in mice with tauopathy. Results IgLON5−/− mice had poorer performance in the wire hang and rotarod tests (which are tests for motor function) than wild-type mice. Moreover, IgLON5−/− mice exhibited decreased anxiety-like behavior and/or hyperactivity in behavior tests, including light/dark transition test and open field test. IgLON5−/− mice also exhibited poorer remote memory in the contextual fear conditioning test. However, neither sleeping disabilities assessed by EEG nor tau aggregation was detected in the knockout mice. Discussion These results suggest that IgLON5 is associated with activity, anxiety, motor ability, and contextual fear memory. Comparing the various phenotypes of anti-IgLON5 disease, antiIgLON5 disease might partially be associated with loss of function of IgLON5; however, other phenotypes, such as sleep disorders and tau aggregation, can be caused by gain of function of IgLON5 and/or neuronal damage due to inflammation. Further studies are needed to elucidate the role of IgLON5 in the pathogenesis of anti-IgLON5 diseases.
AB - Background and Objectives Anti-IgLON5 disease is an autoimmune neurodegenerative disorder characterized by various phenotypes, notably sleep and movement disorders and tau pathology. Although the disease is known to be associated with the neuronal cell adhesion protein IgLON5, the physiologic function of IgLON5 remains elusive. There are conflicting views on whether autoantibodies cause loss of function, activation of IgLON5, or inflammation-associated neuronal damage, ultimately leading to the disease. We generated IgLON5 knockout (−/−) mice to investigate the functions of IgLON5 and elucidate the pathomechanism of anti-IgLON5 disease. Methods IgLON5 knockout (−/−) mice underwent behavioral tests investigating motor function, psychiatric function (notably anxiety and depression), social and exploratory behaviors, spatial learning and memory, and sensory perception. Histologic analysis was conducted to investigate tau aggregation in mice with tauopathy. Results IgLON5−/− mice had poorer performance in the wire hang and rotarod tests (which are tests for motor function) than wild-type mice. Moreover, IgLON5−/− mice exhibited decreased anxiety-like behavior and/or hyperactivity in behavior tests, including light/dark transition test and open field test. IgLON5−/− mice also exhibited poorer remote memory in the contextual fear conditioning test. However, neither sleeping disabilities assessed by EEG nor tau aggregation was detected in the knockout mice. Discussion These results suggest that IgLON5 is associated with activity, anxiety, motor ability, and contextual fear memory. Comparing the various phenotypes of anti-IgLON5 disease, antiIgLON5 disease might partially be associated with loss of function of IgLON5; however, other phenotypes, such as sleep disorders and tau aggregation, can be caused by gain of function of IgLON5 and/or neuronal damage due to inflammation. Further studies are needed to elucidate the role of IgLON5 in the pathogenesis of anti-IgLON5 diseases.
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U2 - 10.1212/NXI.0000000000200234
DO - 10.1212/NXI.0000000000200234
M3 - Article
C2 - 38657185
AN - SCOPUS:85191382071
SN - 2332-7812
VL - 11
JO - Neurology: Neuroimmunology and NeuroInflammation
JF - Neurology: Neuroimmunology and NeuroInflammation
IS - 3
M1 - e200234
ER -