Potential neuron‐autonomous Purkinje cell degeneration by 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase promoter/Cre‐mediated autophagy impairments
| العنوان: | Potential neuron‐autonomous Purkinje cell degeneration by 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase promoter/Cre‐mediated autophagy impairments |
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| المؤلفون: | Hwan Tae Park, Young Hye Kim, Hyeran Kim, Young Rae Jo, Kyung Eun Lee, Yoon Kyung Shin, Da Kyeong Park, Hana Go, Min-Young Song, Yuna Oh, Sung Joong Lee, Juyeon Jo, Sang-Myung Cheon, So Young Jang, Hyun Kyoung Lee |
| المصدر: | The FASEB Journal. 35 |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Purkinje cell, Cre recombinase, Biology, Autophagy-Related Protein 7, Biochemistry, 2',3'-Cyclic-nucleotide 3'-phosphodiesterase, Mice, Purkinje Cells, 03 medical and health sciences, 0302 clinical medicine, 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase, Genetics, medicine, Animals, Molecular Biology, Gene knockout, Mice, Knockout, Integrases, Stem Cells, Neurodegeneration, Gene targeting, Neurodegenerative Diseases, medicine.disease, Cell biology, 030104 developmental biology, medicine.anatomical_structure, nervous system, Neuron, Stem cell, Neuroglia, 030217 neurology & neurosurgery, Biotechnology |
| الوصف: | 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. |
| تدمد: | 1530-6860 0892-6638 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::752f1103f8b3817e4fe64e3e971bddc9 https://doi.org/10.1096/fj.202001366rr |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....752f1103f8b3817e4fe64e3e971bddc9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15306860 08926638 |
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