{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:05:00Z","timestamp":1791317100355,"version":"4.3.1"},"reference-count":26,"publisher":"National Academy of Sciences","issue":"2","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,1,18]]},"abstract":"<jats:p>\n                    We previously generated a mouse model with a mutation in the murine\n                    <jats:italic>Atm<\/jats:italic>\n                    gene that recapitulates many aspects of the childhood neurodegenerative disease ataxia-telangiectasia.\n                    <jats:italic>Atm<\/jats:italic>\n                    -deficient (\n                    <jats:italic>Atm<\/jats:italic>\n                    \u2212\/\u2212) mice show neurological defects detected by motor function tests including the rota-rod, open-field tests and hind-paw footprint analysis. However, no gross histological abnormalities have been observed consistently in the cerebellum of any line of\n                    <jats:italic>Atm<\/jats:italic>\n                    \u2212\/\u2212 mice analyzed in most laboratories. Therefore, it may be that the neurologic dysfunction found in these animals is associated with predegenerative lesions. We performed a detailed analysis of the cerebellar morphology in two independently generated lines of\n                    <jats:italic>Atm<\/jats:italic>\n                    \u2212\/\u2212 mice to determine whether there was evidence of neuronal abnormality. We found a significant increase in the number of lysosomes in\n                    <jats:italic>Atm<\/jats:italic>\n                    \u2212\/\u2212 mice in the absence of any detectable signs of neuronal degeneration or other ultrastructural anomalies. In addition, we found that the ATM protein is predominantly cytoplasmic in Purkinje cells and other neurons, in contrast to the nuclear localization of ATM protein observed in cultured cells. The cytoplasmic localization of ATM in Purkinje cells is similar to that found in human cerebellum. These findings suggest that ATM may be important as a cytoplasmic protein in neurons and that its absence leads to abnormalities of cytoplasmic organelles reflected as an increase in lysosomal numbers.\n                  <\/jats:p>","DOI":"10.1073\/pnas.97.2.871","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:35:07Z","timestamp":1027679707000},"page":"871-876","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":160,"title":["ATM is a cytoplasmic protein in mouse brain required to prevent lysosomal accumulation"],"prefix":"10.1073","volume":"97","author":[{"given":"Carrolee","family":"Barlow","sequence":"first","affiliation":[{"name":"The Salk Institute for Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037; Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, MD 20892; Laboratoire de Neurobiologie Cellulaire, Unit\u00e9 Propre de Recherche 9009 Centre National de la Recherche Scientifique, Centre de Neurochimie, 5 Rue Blaise Pascal, 67084 Strasbourg, France; Department of Neurosciences and Alzheimer Research Laboratory, Case Western Reserve University School..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Ribaut-Barassin","sequence":"additional","affiliation":[{"name":"The Salk Institute for Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037; Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, MD 20892; Laboratoire de Neurobiologie Cellulaire, Unit\u00e9 Propre de Recherche 9009 Centre National de la Recherche Scientifique, Centre de Neurochimie, 5 Rue Blaise Pascal, 67084 Strasbourg, France; Department of Neurosciences and Alzheimer Research Laboratory, Case Western Reserve University School..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa A.","family":"Zwingman","sequence":"additional","affiliation":[{"name":"The Salk Institute for Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037; Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, MD 20892; Laboratoire de Neurobiologie Cellulaire, Unit\u00e9 Propre de Recherche 9009 Centre National de la Recherche Scientifique, Centre de Neurochimie, 5 Rue Blaise Pascal, 67084 Strasbourg, France; Department of Neurosciences and Alzheimer Research Laboratory, Case Western Reserve University School..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amber J.","family":"Pope","sequence":"additional","affiliation":[{"name":"The Salk Institute for Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037; Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, MD 20892; Laboratoire de Neurobiologie Cellulaire, Unit\u00e9 Propre de Recherche 9009 Centre National de la Recherche Scientifique, Centre de Neurochimie, 5 Rue Blaise Pascal, 67084 Strasbourg, France; Department of Neurosciences and Alzheimer Research Laboratory, Case Western Reserve University School..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin D.","family":"Brown","sequence":"additional","affiliation":[{"name":"The Salk Institute for Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037; Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, MD 20892; Laboratoire de Neurobiologie Cellulaire, Unit\u00e9 Propre de Recherche 9009 Centre National de la Recherche Scientifique, Centre de Neurochimie, 5 Rue Blaise Pascal, 67084 Strasbourg, France; Department of Neurosciences and Alzheimer Research Laboratory, Case Western Reserve University School..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennie W.","family":"Owens","sequence":"additional","affiliation":[{"name":"The Salk Institute for Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037; Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, MD 20892; Laboratoire de Neurobiologie Cellulaire, Unit\u00e9 Propre de Recherche 9009 Centre National de la Recherche Scientifique, Centre de Neurochimie, 5 Rue Blaise Pascal, 67084 Strasbourg, France; Department of Neurosciences and Alzheimer Research Laboratory, Case Western Reserve University School..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Larson","sequence":"additional","affiliation":[{"name":"The Salk Institute for Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037; Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, MD 20892; Laboratoire de Neurobiologie Cellulaire, Unit\u00e9 Propre de Recherche 9009 Centre National de la Recherche Scientifique, Centre de Neurochimie, 5 Rue Blaise Pascal, 67084 Strasbourg, France; Department of Neurosciences and Alzheimer Research Laboratory, Case Western Reserve University School..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Harrington","sequence":"additional","affiliation":[{"name":"The Salk Institute for Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037; Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, MD 20892; Laboratoire de Neurobiologie Cellulaire, Unit\u00e9 Propre de Recherche 9009 Centre National de la Recherche Scientifique, Centre de Neurochimie, 5 Rue Blaise Pascal, 67084 Strasbourg, France; Department of Neurosciences and Alzheimer Research Laboratory, Case Western Reserve University School..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Marie","family":"Haeberle","sequence":"additional","affiliation":[{"name":"The Salk Institute for Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037; Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, MD 20892; Laboratoire de Neurobiologie Cellulaire, Unit\u00e9 Propre de Recherche 9009 Centre National de la Recherche Scientifique, Centre de Neurochimie, 5 Rue Blaise Pascal, 67084 Strasbourg, France; Department of Neurosciences and Alzheimer Research Laboratory, Case Western Reserve University School..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Mariani","sequence":"additional","affiliation":[{"name":"The Salk Institute for Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037; Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, MD 20892; Laboratoire de Neurobiologie Cellulaire, Unit\u00e9 Propre de Recherche 9009 Centre National de la Recherche Scientifique, Centre de Neurochimie, 5 Rue Blaise Pascal, 67084 Strasbourg, France; Department of Neurosciences and Alzheimer Research Laboratory, Case Western Reserve University School..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Eckhaus","sequence":"additional","affiliation":[{"name":"The Salk Institute for Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037; Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, MD 20892; Laboratoire de Neurobiologie Cellulaire, Unit\u00e9 Propre de Recherche 9009 Centre National de la Recherche Scientifique, Centre de Neurochimie, 5 Rue Blaise Pascal, 67084 Strasbourg, France; Department of Neurosciences and Alzheimer Research Laboratory, Case Western Reserve University School..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Herrup","sequence":"additional","affiliation":[{"name":"The Salk Institute for Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037; Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, MD 20892; Laboratoire de Neurobiologie Cellulaire, Unit\u00e9 Propre de Recherche 9009 Centre National de la Recherche Scientifique, Centre de Neurochimie, 5 Rue Blaise Pascal, 67084 Strasbourg, France; Department of Neurosciences and Alzheimer Research Laboratory, Case Western Reserve University School..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannick","family":"Bailly","sequence":"additional","affiliation":[{"name":"The Salk Institute for Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037; Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, MD 20892; Laboratoire de Neurobiologie Cellulaire, Unit\u00e9 Propre de Recherche 9009 Centre National de la Recherche Scientifique, Centre de Neurochimie, 5 Rue Blaise Pascal, 67084 Strasbourg, France; Department of Neurosciences and Alzheimer Research Laboratory, Case Western Reserve University School..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Wynshaw-Boris","sequence":"additional","affiliation":[{"name":"The Salk Institute for Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037; Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, MD 20892; Laboratoire de Neurobiologie Cellulaire, Unit\u00e9 Propre de Recherche 9009 Centre National de la Recherche Scientifique, Centre de Neurochimie, 5 Rue Blaise Pascal, 67084 Strasbourg, France; Department of Neurosciences and Alzheimer Research Laboratory, Case Western Reserve University School..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2000,1,18]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.5.1840"},{"key":"e_1_3_3_2_2","first-page":"2707","volume":"13","author":"Lakin N D","year":"1996","unstructured":"N D Lakin, P Weber, T Stankovic, S T Rottinghaus, A M Taylor, S P Jackson Oncogene 13, 2707\u20132716 (1996).","journal-title":"Oncogene"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201037"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.10.1555"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/302223"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80086-0"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.23.13084"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.280.5366.1089"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.19.2411"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.23.12688"},{"key":"e_1_3_3_11_2","volume-title":"Antibodies: A Laboratory Manual","author":"Harlow E","year":"1988","unstructured":"E Harlow, D Lane Antibodies: A Laboratory Manual (Cold Spring Harbor Lab. 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