{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T23:38:38Z","timestamp":1792539518125,"version":"4.5.0"},"reference-count":48,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T00:00:00Z","timestamp":1792540800000},"content-version":"vor","delay-in-days":93,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["KAKENHI 20H03446 and 21H05122"],"award-info":[{"award-number":["KAKENHI 20H03446 and 21H05122"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Japan Agency for Medical Research Development","award":["AMED-LEAP (JP22gm0010006h)"],"award-info":[{"award-number":["AMED-LEAP (JP22gm0010006h)"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-026-62082-5","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T16:25:28Z","timestamp":1784564728000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of a novel glutamate receptor 2 mutation in mice presenting progressive cerebellar ataxia"],"prefix":"10.1038","volume":"16","author":[{"given":"Ayaka","family":"Eguchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natsumi","family":"Maehara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aika","family":"Hirota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuri","family":"Yoshikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Yasuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoko","family":"Arai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Miyazaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"62082_CR1","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1002\/mds.27415","volume":"33","author":"M Rossi","year":"2018","unstructured":"Rossi, M. et al. The genetic nomenclature of recessive cerebellar ataxias. Mov. Disord. 33, 1056\u20131076 (2018).","journal-title":"Mov. Disord."},{"key":"62082_CR2","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1007\/s12311-017-0885-2","volume":"17","author":"MS Salman","year":"2018","unstructured":"Salman, M. S. Epidemiology of cerebellar diseases and therapeutic approaches. Cerebellum 17, 4\u201311 (2018).","journal-title":"Cerebellum"},{"key":"62082_CR3","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2024.1422442","volume":"18","author":"Z-T Cui","year":"2024","unstructured":"Cui, Z.-T. et al. Spinocerebellar ataxias: From pathogenesis to recent therapeutic advances. Front. Neurosci. 18, 1422442 (2024).","journal-title":"Front. Neurosci."},{"key":"62082_CR4","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1007\/s13760-020-01328-z","volume":"121","author":"AC Ceylan","year":"2021","unstructured":"Ceylan, A. C. et al. Autosomal recessive spinocerebellar ataxia 18 caused by homozygous exon 14 duplication in GRID2 and review of the literature. Acta Neurol. Belg. 121, 1457\u20131462 (2021).","journal-title":"Acta Neurol. Belg."},{"key":"62082_CR5","doi-asserted-by":"publisher","first-page":"2838","DOI":"10.1016\/j.celrep.2018.08.022","volume":"24","author":"I Kushima","year":"2018","unstructured":"Kushima, I. et al. Comparative Analyses of Copy-Number Variation in Autism Spectrum Disorder and Schizophrenia Reveal Etiological Overlap and Biological Insights. Cell Rep. 24, 2838\u20132856 (2018).","journal-title":"Cell Rep."},{"key":"62082_CR6","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1177\/1087054720905089","volume":"25","author":"Q Zhang","year":"2021","unstructured":"Zhang, Q. et al. Association of gene variations in ionotropic glutamate receptor and attention-deficit\/hyperactivity disorder in the Chinese population: A two-stage case-control study. J. Atten. Disord. 25, 1362\u20131373 (2021).","journal-title":"J. Atten. Disord."},{"key":"62082_CR7","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aay1769","volume":"12","author":"M-K Pan","year":"2020","unstructured":"Pan, M.-K. et al. Cerebellar oscillations driven by synaptic pruning deficits of cerebellar climbing fibers contribute to tremor pathophysiology. Sci. Transl. Med. 12, eaay1769 (2020).","journal-title":"Sci. Transl. Med."},{"key":"62082_CR8","doi-asserted-by":"publisher","first-page":"1267","DOI":"10.1006\/bbrc.1993.2614","volume":"197","author":"K Araki","year":"1993","unstructured":"Araki, K. et al. Selective expression of the glutamate receptor channel \u03b42 subunit in cerebellar Purkinje cells. Biochem. Biophys. Res. Commun. 197, 1267\u20131276 (1993).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"62082_CR9","doi-asserted-by":"publisher","first-page":"4846","DOI":"10.1523\/JNEUROSCI.0161-16.2016","volume":"36","author":"R Ichikawa","year":"2016","unstructured":"Ichikawa, R., Sakimura, K. & Watanabe, M. GluD2 endows parallel fiber-Purkinje cell synapses with a high regenerative capacity. J. Neurosci. 36, 4846\u20134858 (2016).","journal-title":"J. Neurosci."},{"key":"62082_CR10","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1038\/42009","volume":"388","author":"J Zuo","year":"1997","unstructured":"Zuo, J. et al. Neurodegeneration in Lurcher mice caused by mutation in \u03b42 glutamate receptor gene. Nature 388, 769\u2013773 (1997).","journal-title":"Nature"},{"key":"62082_CR11","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1006\/geno.1998.5314","volume":"50","author":"A Lalouette","year":"1998","unstructured":"Lalouette, A. et al. Hotfoot mouse mutations affect the \u03b42 glutamate receptor gene and are allelic to Lurcher. Genomics 50, 9\u201313 (1998).","journal-title":"Genomics"},{"key":"62082_CR12","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/0092-8674(95)90334-8","volume":"81","author":"N Kashiwabuchi","year":"1995","unstructured":"Kashiwabuchi, N. et al. Impairment of motor coordination, Purkinje cell synapse formation, and cerebellar long-term depression in GluR\u03b42 mutant mice. Cell 81, 245\u2013252 (1995).","journal-title":"Cell"},{"key":"62082_CR13","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/iyae031","volume":"227","author":"R Baldarelli","year":"2024","unstructured":"Baldarelli, R. et al. Mouse genome informatics: An integrated knowledgebase system for the laboratory mouse. Genetics 227, iyae031 (2024).","journal-title":"Genetics"},{"key":"62082_CR14","first-page":"1787","volume":"39","author":"SJ Guyenet","year":"2010","unstructured":"Guyenet, S. J. et al. A simple composite phenotype scoring system for evaluating mouse models of cerebellar ataxia. J. Vis. Exp. 39, 1787 (2010).","journal-title":"J. Vis. Exp."},{"key":"62082_CR15","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giab008","volume":"10","author":"P Danecek","year":"2021","unstructured":"Danecek, P. et al. Twelve years of SAMtools and BCFtools. GigaScience 10, giab008 (2021).","journal-title":"GigaScience"},{"key":"62082_CR16","doi-asserted-by":"crossref","first-page":"D58","DOI":"10.1093\/nar\/gkaa197","volume":"48","author":"T Gao","year":"2020","unstructured":"Gao, T. & Qian, J. EnhancerAtlas 2.0: An updated resource with enhancer annotation in 586 tissue\/cell types across nine species. Nucleic Acids Res. 48, D58\u2013D64 (2020).","journal-title":"Nucleic Acids Res."},{"key":"62082_CR17","doi-asserted-by":"publisher","first-page":"W45","DOI":"10.1093\/nar\/gkae358","volume":"52","author":"Z Zou","year":"2024","unstructured":"Zou, Z., Ohta, T. & Oki, S. ChIP-Atlas 3.0: A data-mining suite to explore chromosome architecture together with large-scale regulome data. Nucleic Acids Res. 52, W45\u2013W53 (2024).","journal-title":"Nucleic Acids Res."},{"key":"62082_CR18","doi-asserted-by":"publisher","DOI":"10.1126\/science.abg4696","volume":"373","author":"I Sarropoulos","year":"2021","unstructured":"Sarropoulos, I. et al. Developmental and evolutionary dynamics of cis-regulatory elements in mouse cerebellar cells. Science 373, eabg4696 (2021).","journal-title":"Science"},{"key":"62082_CR19","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1038\/nmeth.2688","volume":"10","author":"JD Buenrostro","year":"2013","unstructured":"Buenrostro, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y. & Greenleaf, W. J. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10, 1213\u20131218 (2013).","journal-title":"Nat. Methods"},{"key":"62082_CR20","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s13059-014-0560-6","volume":"16","author":"M Lizio","year":"2015","unstructured":"Lizio, M. et al. Gateways to the FANTOM5 promoter level mammalian expression atlas. Genome Biol. 16, 22 (2015).","journal-title":"Genome Biol."},{"key":"62082_CR21","doi-asserted-by":"publisher","first-page":"D892","DOI":"10.1093\/nar\/gkaa1054","volume":"49","author":"I Abugessaisa","year":"2021","unstructured":"Abugessaisa, I. et al. FANTOM enters 20th year: Expansion of transcriptomic atlases and functional annotation of non-coding RNAs. Nucleic Acids Res. 49, D892\u2013D898 (2021).","journal-title":"Nucleic Acids Res."},{"key":"62082_CR22","doi-asserted-by":"publisher","first-page":"D88","DOI":"10.1093\/nar\/gkl822","volume":"35","author":"A Visel","year":"2007","unstructured":"Visel, A., Minovitsky, S., Dubchak, I. & Pennacchio, L. A. VISTA enhancer browser\u2014a database of tissue-specific human enhancers. Nucleic Acids Res. 35, D88\u2013D92 (2007).","journal-title":"Nucleic Acids Res."},{"key":"62082_CR23","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.74207","volume":"11","author":"M Ramirez","year":"2022","unstructured":"Ramirez, M. et al. Temporal analysis of enhancers during mouse cerebellar development reveals dynamic and novel regulatory functions. Elife 11, e74207 (2022).","journal-title":"Elife"},{"key":"62082_CR24","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1093\/bioinformatics\/btv710","volume":"32","author":"X Chen","year":"2016","unstructured":"Chen, X. et al. Manta: Rapid detection of structural variants and indels for germline and cancer sequencing applications. Bioinformatics 32, 1220\u20131222 (2016).","journal-title":"Bioinformatics"},{"key":"62082_CR25","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0107867","volume":"9","author":"Y Miyoshi","year":"2014","unstructured":"Miyoshi, Y. et al. A new mouse allele of glutamate receptor delta 2 with cerebellar atrophy and progressive ataxia. PLoS ONE 9, e107867 (2014).","journal-title":"PLoS ONE"},{"key":"62082_CR26","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/j.cub.2021.11.052","volume":"32","author":"X Liu","year":"2022","unstructured":"Liu, X. et al. A single-nucleotide mutation within the TBX3 enhancer increased body size in Chinese horses. Curr. Biol. 32, 480-487.e6 (2022).","journal-title":"Curr. Biol."},{"key":"62082_CR27","doi-asserted-by":"publisher","first-page":"D229","DOI":"10.1093\/nar\/gkx1001","volume":"46","author":"A Suzuki","year":"2018","unstructured":"Suzuki, A. et al. DBTSS\/DBKERO for integrated analysis of transcriptional regulation. Nucleic Acids Res. 46, D229\u2013D238 (2018).","journal-title":"Nucleic Acids Res."},{"key":"62082_CR28","doi-asserted-by":"publisher","first-page":"2519","DOI":"10.1016\/j.molcel.2022.04.009","volume":"82","author":"M Martinez-Ara","year":"2022","unstructured":"Martinez-Ara, M., Comoglio, F., van Arensbergen, J. & van Steensel, B. Systematic analysis of intrinsic enhancer-promoter compatibility in the mouse genome. Mol. Cell 82, 2519-2531.e6 (2022).","journal-title":"Mol. Cell"},{"key":"62082_CR29","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1038\/nrg3207","volume":"13","author":"F Spitz","year":"2012","unstructured":"Spitz, F. & Furlong, E. E. M. Transcription factors: From enhancer binding to developmental control. Nat. Rev. Genet. 13, 613\u2013626 (2012).","journal-title":"Nat. Rev. Genet."},{"key":"62082_CR30","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1016\/j.nbd.2008.10.013","volume":"33","author":"T Seki","year":"2009","unstructured":"Seki, T. et al. Mutant \u03b3PKC found in spinocerebellar ataxia type 14 induces aggregate-independent maldevelopment of dendrites in primary cultured Purkinje cells. Neurobiol. Dis. 33, 260\u2013273 (2009).","journal-title":"Neurobiol. Dis."},{"key":"62082_CR31","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1007\/s12311-015-0748-7","volume":"15","author":"HS Zanjani","year":"2016","unstructured":"Zanjani, H. S., Vogel, M. W. & Mariani, J. Deletion of the GluR\u03b42 receptor in the hotfoot mouse mutant causes granule cell loss, delayed Purkinje cell death, and reductions in Purkinje cell dendritic tree area. Cerebellum 15, 755\u2013766 (2016).","journal-title":"Cerebellum"},{"key":"62082_CR32","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-10-65","volume":"10","author":"B Vernet-der Garabedian","year":"2013","unstructured":"Vernet-der Garabedian, B., Derer, P., Bailly, Y. & Mariani, J. Innate immunity in the Grid2Lc\/+mouse model of cerebellar neurodegeneration: Glial CD95\/CD95L plays a non-apoptotic role in persistent neuron loss-associated inflammatory reactions in the cerebellum. J. Neuroinflammation 10, 829 (2013).","journal-title":"J. Neuroinflammation"},{"key":"62082_CR33","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1046\/j.1460-9568.2003.02595.x","volume":"17","author":"Y Wang","year":"2003","unstructured":"Wang, Y. et al. A hot spot for hotfoot mutations in the gene encoding the \u03b42 glutamate receptor. Eur. J. Neurosci. 17, 1581\u20131590 (2003).","journal-title":"Eur. J. Neurosci."},{"key":"62082_CR34","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1038\/nature03060","volume":"432","author":"N Amrani","year":"2004","unstructured":"Amrani, N. et al. A faux 3\u2032-UTR promotes aberrant termination and triggers nonsense- mediated mRNA decay. Nature 432, 112\u2013118 (2004).","journal-title":"Nature"},{"key":"62082_CR35","unstructured":"Andrews, S. FastQC: A quality control tool for high throughput sequence data. Babraham Bioinformatics https:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc\/ (2023)."},{"key":"62082_CR36","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","volume":"30","author":"AM Bolger","year":"2014","unstructured":"Bolger, A. M., Lohse, M. & Usadel, B. Trimmomatic: A flexible trimmer for Illumina sequence data. Bioinformatics 30, 2114\u20132120 (2014).","journal-title":"Bioinformatics"},{"key":"62082_CR37","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","volume":"25","author":"H Li","year":"2009","unstructured":"Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25, 1754\u20131760 (2009).","journal-title":"Bioinformatics"},{"key":"62082_CR38","unstructured":"Broad Institute. Picard Toolkit. GitHub Repository https:\/\/broadinstitute.github.io\/picard\/ (2019)."},{"key":"62082_CR39","first-page":"35","volume":"3","author":"P Cingolani","year":"2012","unstructured":"Cingolani, P. et al. Using drosophila melanogaster as a model for genotoxic chemical mutational studies with a new program. SnpSift. Front. Genet. 3, 35 (2012).","journal-title":"SnpSift. Front. Genet."},{"key":"62082_CR40","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/nbt.1754","volume":"29","author":"JT Robinson","year":"2011","unstructured":"Robinson, J. T. et al. Integrative genomics viewer. Nat. Biotechnol. 29, 24\u201326 (2011).","journal-title":"Nat. Biotechnol."},{"key":"62082_CR41","doi-asserted-by":"publisher","DOI":"10.3389\/fbinf.2022.818619","volume":"2","author":"MW Davis","year":"2022","unstructured":"Davis, M. W. & Jorgensen, E. M. ApE, a plasmid editor: A freely available DNA manipulation and visualization program. Front. Bioinform. 2, 818619 (2022).","journal-title":"Front. Bioinform."},{"key":"62082_CR42","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","volume":"37","author":"D Kim","year":"2019","unstructured":"Kim, D., Paggi, J. M., Park, C., Bennett, C. & Salzberg, S. L. Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nat. Biotechnol. 37, 907\u2013915 (2019).","journal-title":"Nat. Biotechnol."},{"key":"62082_CR43","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/nbt.3122","volume":"33","author":"M Pertea","year":"2015","unstructured":"Pertea, M. et al. StringTie enables improved reconstruction of a transcriptome from RNA-seq reads. Nat. Biotechnol. 33, 290\u2013295 (2015).","journal-title":"Nat. Biotechnol."},{"key":"62082_CR44","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","volume":"26","author":"MD Robinson","year":"2010","unstructured":"Robinson, M. D., McCarthy, D. J. & Smyth, G. K. EdgeR: A Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139\u2013140 (2010).","journal-title":"Bioinformatics"},{"key":"62082_CR45","doi-asserted-by":"publisher","first-page":"E5593","DOI":"10.1073\/pnas.1419161111","volume":"111","author":"S Shen","year":"2014","unstructured":"Shen, S. et al. rMATS: Robust and flexible detection of differential alternative splicing from replicate RNA-Seq data. Proc. Natl. Acad. Sci. U. S. A. 111, E5593\u2013E5601 (2014).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"62082_CR46","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","volume":"20","author":"A McKenna","year":"2010","unstructured":"McKenna, A. et al. The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297\u20131303 (2010).","journal-title":"Genome Res."},{"key":"62082_CR47","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/j.neuron.2014.05.039","volume":"83","author":"T Yamada","year":"2014","unstructured":"Yamada, T. et al. Promoter decommissioning by the NuRD chromatin remodeling complex triggers synaptic connectivity in the mammalian brain. Neuron 83, 122\u2013134 (2014).","journal-title":"Neuron"},{"key":"62082_CR48","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1007\/BF01175119","volume":"5","author":"IA Hendry","year":"1976","unstructured":"Hendry, I. A. A method to correct adequately for the change in neuronal size when estimating neuronal numbers after nerve growth factor treatment. J. Neurocytol. 5, 337\u2013349 (1976).","journal-title":"J. Neurocytol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-62082-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-62082-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-62082-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T22:48:53Z","timestamp":1792536533000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-026-62082-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":48,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["62082"],"URL":"https:\/\/doi.org\/10.1038\/s41598-026-62082-5","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,20]]},"assertion":[{"value":"10 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 July 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 July 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"33076"}}