Potential neuron-autonomous Purkinje cell degeneration by 2 ',3 '-cyclic nucleotide 3 '-phosphodiesterase promoter/Cre-mediated autophagy impairments

Authors
Jo, Young RaeKim, Hye RanJang, So YoungGo, HanaSong, Min-YoungPark, Da KyeongOh, YunaJo, JuyeonShin, Yoon KyungLee, Sung JoongCheon, Sang-MyungLee, Hyun KyoungLee, Kyung EunKim, Young HyePark, Hwan Tae
Issue Date
2021-01
Publisher
WILEY
Citation
FASEB JOURNAL, v.35, no.1
Abstract
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.
Keywords
ALPHA-SYNUCLEIN; MOUSE MODEL; OLIGODENDROCYTES; MYELIN; EXPRESSION; PROTEIN; CNP; ALPHA-SYNUCLEIN; MOUSE MODEL; OLIGODENDROCYTES; MYELIN; EXPRESSION; PROTEIN; CNP; CNP; myelination; neurodegeneration; oligodendrocyte; p62
ISSN
0892-6638
URI
https://pubs.kist.re.kr/handle/201004/117575
DOI
10.1096/fj.202001366RR
Appears in Collections:
KIST Article > 2021
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE