{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T13:33:10Z","timestamp":1777555990917,"version":"3.51.4"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2018,7,1]],"date-time":"2018-07-01T00:00:00Z","timestamp":1530403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Human Ag R (HuR) is an RNA binding protein in the ELAVL protein family. To study the neuron-specific function of HuR, we generated inducible, neuron-specific HuR-deficient mice of both sexes. After tamoxifen-induced deletion of HuR, these mice developed a phenotype consisting of poor balance, decreased movement, and decreased strength. They performed significantly worse on the rotarod test compared with littermate control mice, indicating coordination deficiency. Using the grip-strength test, it was also determined that the forelimbs of neuron-specific HuR-deficient mice were much weaker than littermate control mice. Immunostaining of the brain and cervical spinal cord showed that HuR-deficient neurons had increased levels of cleaved caspase-3, a hallmark of cell apoptosis. Caspase-3 cleavage was especially strong in pyramidal neurons and \u03b1 motor neurons of HuR-deficient mice. Genome-wide microarray and real-time PCR analysis further indicated that HuR deficiency in neurons resulted in altered expression of genes in the brain involved in cell growth, including trichoplein keratin filament\u2013binding protein, Cdkn2c, G-protein signaling modulator 2, immediate early response 2, superoxide dismutase 1, and Bcl2. The additional enriched Gene Ontology terms in the brain tissues of neuron-specific HuR-deficient mice were largely related to inflammation, including IFN-induced genes and complement components. Importantly, some of these HuR-regulated genes were also significantly altered in the brain and spinal cord of patients with amyotrophic lateral sclerosis. Additionally, neuronal HuR deficiency resulted in the redistribution of TDP43 to cytosolic granules, which has been linked to motor neuron disease. Taken together, we propose that this neuron-specific HuR-deficient mouse strain can potentially be used as a motor neuron disease model.<\/jats:p>","DOI":"10.4049\/jimmunol.1701501","type":"journal-article","created":{"date-parts":[[2018,5,14]],"date-time":"2018-05-14T15:15:19Z","timestamp":1526310919000},"page":"157-166","source":"Crossref","is-referenced-by-count":19,"title":["Neuron-Specific HuR-Deficient Mice Spontaneously Develop Motor Neuron Disease"],"prefix":"10.1093","volume":"201","author":[{"given":"Kevin","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Biology, University of Pennsylvania , Philadelphia, PA 19104"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Genetics, Stanford University School of Medicine , Stanford, CA 94305"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Immunology, Cleveland Clinic , Cleveland, OH 44195"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Immunology, Cleveland Clinic , Cleveland, OH 44195"},{"name":"Department of Pharmacology, School of Medicine, Southeast University , Nanjing 210009, Jiangsu ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2032-5294","authenticated-orcid":false,"given":"Gao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Genetics, Stanford University School of Medicine , Stanford, CA 94305"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga N","family":"Kokiko-Cochran","sequence":"additional","affiliation":[{"name":"The Ohio State University, Wexner Medical Center , Columbus, OH 43210"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8507-2561","authenticated-orcid":false,"given":"Bruce","family":"Lamb","sequence":"additional","affiliation":[{"name":"Stark Neurosciences Research Institute, Indiana University , Bloomington, IN 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9817-242X","authenticated-orcid":false,"given":"Thomas A","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Department of Immunology, Cleveland Clinic , Cleveland, OH 44195"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching-Yi","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Cleveland Clinic , Cleveland, OH 44195"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Shang","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Cleveland Clinic , Cleveland, OH 44195"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomasz","family":"Herjan","sequence":"additional","affiliation":[{"name":"Department of Immunology, Cleveland Clinic , Cleveland, OH 44195"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,7,1]]},"reference":[{"key":"2025030417570100200_r1","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nature20413","article-title":"Decoding ALS: from genes to mechanism","volume":"539","author":"Taylor","year":"2016","journal-title":"Nature"},{"key":"2025030417570100200_r2","doi-asserted-by":"crossref","first-page":"171","DOI":"10.4103\/2152-7806.169561","article-title":"A comprehensive review of amyotrophic lateral sclerosis","volume":"6","author":"Zarei","year":"2015","journal-title":"Surg. 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