Potential neuron-autonomous Purkinje cell degeneration by 2',3'-cyclic nucleotide 3'-phosphodiesterase promoter/Cre-mediated autophagy impairments.
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.
['Jo|Young Rae|YR|', 'Kim|Hye Ran|HR|', 'Jang|So Young|SY|', 'Go|Hana|H|', 'Song|Min-Young|MY|', 'Park|Da Kyeong|DK|', 'Oh|Yuna|Y|', 'Jo|Juyeon|J|', 'Shin|Yoon Kyung|YK|', 'Lee|Sung Joong|SJ|', 'Cheon|Sang-Myung|SM|', 'Lee|Hyun Kyoung|HK|', 'Lee|Kyung Eun|KE|', 'Kim|Young Hye|YH|', 'Park|Hwan Tae|HT|']
D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase D000818:Animals D000071193:Autophagy-Related Protein 7 D019426:Integrases D051379:Mice D018345:Mice, Knockout D019636:Neurodegenerative Diseases D009457:Neuroglia D011689:Purkinje Cells D013234:Stem Cells
CNP oligodendrocyte p62 neurodegeneration myelination