Jo, Young Rae Kim, Hye Ran Jang, So Young Go, Hana Song, Min-Young Park, Da Kyeong Oh, Yuna Jo, Juyeon Shin, Yoon Kyung Lee, Sung Joong Cheon, Sang-Myung Lee, Hyun Kyoung Lee, Kyung Eun Kim, Young Hye Park, Hwan Tae 2024-01-19T15:33:56Z 2024-01-19T15:33:56Z 2022-01-10 2021-01 0892-6638 https://pubs.kist.re.kr/handle/201004/117575 Studies of neuroglial interaction largely depend on cell-specific gene knockout (KO) experiments using Cre recombinase. However, genes known as glial-specific genes have recently been reported to be expressed in neuroglial stem cells, leading to the possibility that a glia-specific Cre driver results in unwanted gene deletion in neurons, which may affect sound interpretation. 2 ',3 '-Cyclic nucleotide 3 '-phosphodiesterase (CNP) is generally considered to be an oligodendrocyte (OL) marker. Accordingly, Cnp promoter-controlled Cre recombinase has been used to create OL-specific gene targeting mice. However, in this study, using Rosa26-tdTomato-reporter/Cnp-Cre mice, we found that many forebrain neurons and cerebellar Purkinje neurons belong to the lineages of Cnp-expressing neuroglial stem cells. To answer whether gene targeting by Cnp-Cre can induce neuron-autonomous defects, we conditionally deleted an essential autophagy gene, Atg7, in Cnp-Cre mice. The Cnp-Cre-mediated Atg7 KO mice showed extensive p62 inclusion in neurons, including cerebellar Purkinje neurons with extensive neurodegeneration. Furthermore, neuronal areas showing p62 inclusion in Cnp-Cre-mediated Atg7 KO mice overlapped with the neuronal lineage of Cnp-expressing neuroglial stem cells. Moreover, Cnp-Cre-mediated Atg7-KO mice did not develop critical defects in myelination. Our results demonstrate that a large population of central neurons are derived from Cnp-expressing neuroglial stem cells; thus, conditional gene targeting using the Cnp promoter, which is known to be OL-specific, can induce neuron-autonomous phenotypes. English WILEY ALPHA-SYNUCLEIN MOUSE MODEL OLIGODENDROCYTES MYELIN EXPRESSION PROTEIN CNP Potential neuron-autonomous Purkinje cell degeneration by 2 ',3 '-cyclic nucleotide 3 '-phosphodiesterase promoter/Cre-mediated autophagy impairments Article 10.1096/fj.202001366RR 1 FASEB JOURNAL, v.35, no.1 FASEB JOURNAL 35 1 scie scopus 000605626600036 2-s2.0-85098529819 Biochemistry & Molecular Biology Biology Cell Biology Biochemistry & Molecular Biology Life Sciences & Biomedicine - Other Topics Cell Biology Article ALPHA-SYNUCLEIN MOUSE MODEL OLIGODENDROCYTES MYELIN EXPRESSION PROTEIN CNP CNP myelination neurodegeneration oligodendrocyte p62