@article{oai:repository.lib.tottori-u.ac.jp:00004606, author = {香月, 康宏 and Kazuki, Yasuhiro and 平塚, 正治 and Hiratsuka, Masaharu and Togai, Shota and Hamamichi, Shusei}, issue = {1}, journal = {Yonago Acta Medica, Yonago Acta Medica}, month = {Feb}, note = {Background: Cytoplasmic mislocalization of TAR-DNA binding protein of 43 kDa (TDP-43) is a major hallmark of amyotrophic lateral sclerosis (ALS). TDP-43 aggregation is detected in the cortical and spinal motor neurons in most ALS cases; however, pathological mechanism of this mislocalized TDP-43 remains unknown. Methods: We generated a tetracycline-inducible TDP-43 A315T system on a mouse artificial chromosome (MAC) vector to avoid transgene-insertional mutagenesis, established a mouse embryonic stem (ES) cell line holding this MAC vector system, and investigated whether overexpressed exogenous TDP-43 A315T was mislocalized in the cytoplasm of the ES cell-derived neurons and triggered the neurotoxic effects on these cells. Results: Inducible TDP-43 A315T system was successfully loaded onto the MAC and introduced into the mouse ES cells. These ES cells could differentiate into motor neurons and interneurons. Overexpression of TDP-43 A315T by addition of doxycycline in both neurons resulted in mislocalization to cytoplasm. Mislocalized TDP-43 caused cell death of motor neurons, but not interneurons. Conclusion: Vulnerability to cytoplasmic mislocalized TDP-43 is selective on neuronal types, whereas mislocalization of overexpressed TDP-43 occurs in even insusceptible neurons. This inducible gene expression system using MAC remains useful for providing critical insights into appearance of TDP-43 pathology.}, pages = {24--35}, title = {Pathological Comparison of TDP-43 Between Motor Neurons and Interneurons Expressed by a Tetracycline Repressor System on the Mouse Artificial Chromosome}, volume = {66}, year = {2023}, yomi = {カズキ, ヤスヒロ and ヒラツカ, マサハル} }