{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T19:38:14Z","timestamp":1777491494798,"version":"3.51.4"},"reference-count":51,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,6,6]],"date-time":"2019-06-06T00:00:00Z","timestamp":1559779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81671253"],"award-info":[{"award-number":["81671253"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81471157"],"award-info":[{"award-number":["81471157"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BE2016765"],"award-info":[{"award-number":["BE2016765"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National 973 Basic Research Program of China","award":["2014CB943303"],"award-info":[{"award-number":["2014CB943303"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Williams-Beuren syndrome (WBS) is caused by microdeletions of 28 genes and is characterized by cognitive disorder and hypotrophic corpus callosum (CC). Nsun5 gene, which encodes cytosine-5 RNA methyltransferase, is located in the deletion loci of WBS. We have reported that single-gene knockout of Nsun5 (Nsun5-KO) in mice impairs spatial cognition. Herein, we report that postnatal day (PND) 60 Nsun5-KO mice showed the volumetric reduction of CC with a decline in the number of myelinated axons and loose myelin sheath. Nsun5 was highly expressed in callosal oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs) from PND7 to PND28. The numbers of OPCs and OLs in CC of PND7-28 Nsun5-KO mice were significantly reduced compared to wild-type littermates. Immunohistochemistry and Western blot analyses of myelin basic protein (MBP) showed the hypomyelination in the CC of PND28 Nsun5-KO mice. The Nsun5 deletion suppressed the proliferation of OPCs but did not affect transition of radial glial cells into OPCs or cell cycle exit of OPCs. The protein levels, rather than transcriptional levels, of CDK1, CDK2 and Cdc42 in the CC of PND7 and PND14 Nsun5-KO mice were reduced. These findings point to the involvement of Nsun5 deletion in agenesis of CC observed in WBS.<\/jats:p>","DOI":"10.3390\/cells8060552","type":"journal-article","created":{"date-parts":[[2019,6,7]],"date-time":"2019-06-07T03:56:31Z","timestamp":1559879791000},"page":"552","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Agenesis and Hypomyelination of Corpus Callosum in Mice Lacking Nsun5, an RNA Methyltransferase"],"prefix":"10.3390","volume":"8","author":[{"given":"Zihao","family":"Yuan","sequence":"first","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine, Department of Physiology, Nanjing Medical University, Nanjing 211166, China"},{"name":"Department of Physiology, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peipei","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine, Department of Physiology, Nanjing Medical University, Nanjing 211166, China"},{"name":"Department of Physiology, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingting","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine, Department of Physiology, Nanjing Medical University, Nanjing 211166, China"},{"name":"Department of Physiology, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Shen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine, Department of Physiology, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Reproductive Medicine, Department of Physiology, Nanjing Medical University, Nanjing 211166, China"},{"name":"Department of Physiology, Nanjing Medical University, Nanjing 211166, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1056\/NEJMra0903074","article-title":"Williams-Beuren syndrome","volume":"362","author":"Pober","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/ng0993-11","article-title":"Hemizygosity at the elastin locus in a developmental disorder, Williams syndrome","volume":"5","author":"Ewart","year":"1993","journal-title":"Nat. Genet."},{"key":"ref_3","first-page":"46","article-title":"Clinical characterization, molecular and FISH studies in 80 patients with clinical suspicion of Williams-Beuren syndrome","volume":"113","author":"Mila","year":"1999","journal-title":"Med. Clin. (Barc)"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"7079","DOI":"10.1523\/JNEUROSCI.17-18-07079.1997","article-title":"Structural and functional analyses of human cerebral cortex using a surface-based atlas","volume":"17","author":"Drury","year":"1997","journal-title":"J. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1097\/WNR.0b013e3280115942","article-title":"Callosal morphology in Williams syndrome: A new evaluation of shape and thickness","volume":"18","author":"Luders","year":"2007","journal-title":"Neuroreport"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/ejhg.2008.42","article-title":"Dysmorphic features, simplified gyral pattern and 7q11.23 duplication reciprocal to the Williams-Beuren deletion","volume":"16","author":"Torniero","year":"2008","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1111\/j.1469-8749.2001.tb00180.x","article-title":"Corpus callosum morphology of Williams syndrome: Relation to genetics and behavior","volume":"43","author":"Schmitt","year":"2001","journal-title":"Dev. Med. Child. Neurol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1089\/neu.2005.22.76","article-title":"Changes in white matter in long-term survivors of severe non-missile traumatic brain injury: A computational analysis of magnetic resonance images","volume":"22","author":"Tomaiuolo","year":"2005","journal-title":"J. Neurotrauma"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1111\/jir.12457","article-title":"7q11.23 microduplication syndrome: Neurophysiological and neuroradiological insights into a rare chromosomal disorder","volume":"62","author":"Castiglia","year":"2018","journal-title":"J. Intellect Disabil. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1007\/s00018-008-8401-y","article-title":"The genomic basis of the Williams-Beuren syndrome","volume":"66","author":"Schubert","year":"2009","journal-title":"Cell Mol. Life Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9062","DOI":"10.1093\/nar\/gkt679","article-title":"Yeast Nop2 and Rcm1 methylate C2870 and C2278 of the 25S rRNA, respectively","volume":"41","author":"Sharma","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1261\/rna.043398.113","article-title":"A cluster of methylations in the domain IV of 25S rRNA is required for ribosome stability","volume":"20","author":"Gigova","year":"2014","journal-title":"RNA"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Schosserer, M., Minois, N., Angerer, T.B., Amring, M., Dellago, H., Harreither, E., Calle-Perez, A., Pircher, A., Gerstl, M.P., and Pfeifenberger, S. (2015). Methylation of ribosomal RNA by NSUN5 is a conserved mechanism modulating organismal lifespan. Nat. Commun., 6.","DOI":"10.1038\/ncomms7158"},{"key":"ref_14","unstructured":"Zhang, T., Chen, P., Li, W., Sha, S., Wang, Y., Yuan, Z., Shen, B., and Chen, L. (2018). Cognitive deficits in mice lacking Nsun5, a cytosine-5 RNA methyltransferase, with impairment of oligodendrocyte precursor cells. Glia."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1152\/physrev.2001.81.2.871","article-title":"Biology of oligodendrocyte and myelin in the mammalian central nervous system","volume":"81","author":"Baumann","year":"2001","journal-title":"Physiol. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/S0166-2236(00)01691-X","article-title":"The oligodendrocyte precursor cell in health and disease","volume":"24","author":"Levine","year":"2001","journal-title":"Trends Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1126\/science.1190927","article-title":"Regulation of oligodendrocyte differentiation and myelination","volume":"330","author":"Emery","year":"2010","journal-title":"Science"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/nrn2797","article-title":"Myelination and the trophic support of long axons","volume":"11","author":"Nave","year":"2010","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1038\/nmeth.2857","article-title":"Efficient genome modification by CRISPR-Cas9 nickase with minimal off-target effects","volume":"11","author":"Shen","year":"2014","journal-title":"Nat. Methods"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Giera, S., Deng, Y., Luo, R., Ackerman, S.D., Mogha, A., Monk, K.R., Ying, Y., Jeong, S.J., Makinodan, M., and Bialas, A.R. (2015). The adhesion G protein-coupled receptor GPR56 is a cell-autonomous regulator of oligodendrocyte development. Nat. Commun., 6.","DOI":"10.1038\/ncomms7121"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"15764","DOI":"10.1523\/JNEUROSCI.2267-14.2014","article-title":"Oligodendrocyte precursor cell-intrinsic effect of Rheb1 controls differentiation and mediates mTORC1-dependent myelination in brain","volume":"34","author":"Zou","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/nature12647","article-title":"A regenerative approach to the treatment of multiple sclerosis","volume":"502","author":"Deshmukh","year":"2013","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7004","DOI":"10.1523\/JNEUROSCI.0288-05.2005","article-title":"Region-specific myelin pathology in mice lacking the golli products of the myelin basic protein gene","volume":"25","author":"Jacobs","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1007\/s10585-010-9336-x","article-title":"Individual and combined soy isoflavones exert differential effects on metastatic cancer progression","volume":"27","author":"Martinez","year":"2010","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2716","DOI":"10.1210\/me.2008-0255","article-title":"Overexpression of pre-pro-cholecystokinin stimulates beta-cell proliferation in mouse and human islets with retention of islet function","volume":"22","author":"Lavine","year":"2008","journal-title":"Mol. Endocrinol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.18632\/aging.101032","article-title":"The progeroid gene BubR1 regulates axon myelination and motor function","volume":"8","author":"Choi","year":"2016","journal-title":"Aging (Albany NY)"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1083\/jcb.200702031","article-title":"Cdk2 is critical for proliferation and self-renewal of neural progenitor cells in the adult subventricular zone","volume":"179","author":"Jablonska","year":"2007","journal-title":"J. Cell Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"8553","DOI":"10.1523\/JNEUROSCI.22-19-08553.2002","article-title":"Cyclin-dependent kinase-2 controls oligodendrocyte progenitor cell cycle progression and is downregulated in adult oligodendrocyte progenitors","volume":"22","author":"Belachew","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1002\/neu.1066","article-title":"Tyrosine phosphorylation of p190 RhoGAP by Fyn regulates oligodendrocyte differentiation","volume":"49","author":"Wolf","year":"2001","journal-title":"J. Neurobiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1146\/annurev.cellbio.13.1.261","article-title":"Cyclin-dependent kinases: Engines, clocks and microprocessors","volume":"13","author":"Morgan","year":"1997","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/ng1232","article-title":"Cyclin-dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice","volume":"35","author":"Ortega","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1038\/ncb1284","article-title":"Cdc2-cyclin E complexes regulate the G1\/S phase transition","volume":"7","author":"Aleem","year":"2005","journal-title":"Nat. Cell Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/35048096","article-title":"Mitotic kinases as regulators of cell division and its checkpoints","volume":"2","author":"Nigg","year":"2001","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4344","DOI":"10.1073\/pnas.95.8.4344","article-title":"Cyclin B2-null mice develop normally and are fertile whereas cyclin B1-null mice die in utero","volume":"95","author":"Brandeis","year":"1998","journal-title":"Proc. Natl. Acad Sci. USA"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Jablonska, B., Gierdalski, M., Chew, L.J., Hawley, T., Catron, M., Lichauco, A., Cabrera-Luque, J., Yuen, T., Rowitch, D., and Gallo, V. (2016). Sirt1 regulates glial progenitor proliferation and regeneration in white matter after neonatal brain injury. Nat. Commun., 7.","DOI":"10.1038\/ncomms13866"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2030","DOI":"10.1093\/nar\/gkx1255","article-title":"PolyC-binding proteins enhance expression of the CDK2 cell cycle regulatory protein via alternative splicing","volume":"46","author":"Ji","year":"2018","journal-title":"Nucleic. Acids Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1083\/jcb.201004146","article-title":"Cdk2 loss accelerates precursor differentiation and remyelination in the adult central nervous system","volume":"193","author":"Caillava","year":"2011","journal-title":"J. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1016\/j.cub.2003.09.024","article-title":"Cdk2 knockout mice are viable","volume":"13","author":"Berthet","year":"2003","journal-title":"Curr. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1038\/nsmb.2357","article-title":"RNA cytosine methylation by Dnmt2 and NSun2 promotes tRNA stability and protein synthesis","volume":"19","author":"Tuorto","year":"2012","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.cub.2006.04.027","article-title":"The RNA methyltransferase Misu (NSun2) mediates Myc-induced proliferation and is upregulated in tumors","volume":"16","author":"Frye","year":"2006","journal-title":"Curr. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4043","DOI":"10.1128\/MCB.00742-15","article-title":"NSun2 Promotes Cell Growth via Elevating Cyclin-Dependent Kinase 1 Translation","volume":"35","author":"Xing","year":"2015","journal-title":"Mol. Cell Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/j.cell.2014.04.052","article-title":"Oligodendrocyte-encoded HIF function couples postnatal myelination and white matter angiogenesis","volume":"158","author":"Yuen","year":"2014","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0092-8674(02)00678-5","article-title":"Common developmental requirement for Olig function indicates a motor neuron\/oligodendrocyte connection","volume":"109","author":"Lu","year":"2002","journal-title":"Cell"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1523\/JNEUROSCI.4717-05.2006","article-title":"A critical role for dorsal progenitors in cortical myelination","volume":"26","author":"Yue","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1242\/dev.018234","article-title":"Netrin 1 and Dcc regulate oligodendrocyte process branching and membrane extension via Fyn and RhoA","volume":"136","author":"Rajasekharan","year":"2009","journal-title":"Development"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"7140","DOI":"10.1523\/JNEUROSCI.5319-03.2004","article-title":"Signaling from integrins to Fyn to Rho family GTPases regulates morphologic differentiation of oligodendrocytes","volume":"24","author":"Liang","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"10110","DOI":"10.1523\/JNEUROSCI.2158-06.2006","article-title":"Cdc42 and Rac1 signaling are both required for and act synergistically in the correct formation of myelin sheaths in the CNS","volume":"26","author":"Thurnherr","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/nature11314","article-title":"Oligodendroglia metabolically support axons and contribute to neurodegeneration","volume":"487","author":"Lee","year":"2012","journal-title":"Nature"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S0093-934X(03)00062-2","article-title":"Communicative deficits in agenesis of the corpus callosum: Nonliteral language and affective prosody","volume":"85","author":"Paul","year":"2003","journal-title":"Brain Lang."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1136\/jmg.40.2.136","article-title":"Using case study comparisons to explore genotype-phenotype correlations in Williams-Beuren syndrome","volume":"40","author":"Grant","year":"2003","journal-title":"J. Med. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"6481","DOI":"10.1093\/hmg\/ddu368","article-title":"Heterozygous deletion of the Williams-Beuren syndrome critical interval in mice recapitulates most features of the human disorder","volume":"23","author":"Sahun","year":"2014","journal-title":"Hum. Mol. Genet."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/6\/552\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:56:45Z","timestamp":1760187405000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/8\/6\/552"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,6]]},"references-count":51,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2019,6]]}},"alternative-id":["cells8060552"],"URL":"https:\/\/doi.org\/10.3390\/cells8060552","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,6]]}}}