{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T04:52:59Z","timestamp":1791089579804,"version":"4.1.0"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"25","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,6,20]]},"abstract":"<jats:p>\n                    ALS2 is an autosomal recessive form of spastic paraparesis (motor neuron disease) with juvenile onset and slow progression caused by loss of function of alsin, an activator of Rac1 and Rab5 small GTPases. To establish an animal model of ALS2 and derive insights into the pathogenesis of this illness, we have generated alsin-null mice. Cytosol from brains of\n                    <jats:italic>Als2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice shows marked diminution of Rab5-dependent endosome fusion activity. Furthermore, primary neurons from\n                    <jats:italic>Als2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice show a disturbance in endosomal transport of insulin-like growth factor 1 (IGF1) and BDNF receptors, whereas neuronal viability and endocytosis of transferrin and dextran seem unaltered. There is a significant decrease in the size of cortical motor neurons, and\n                    <jats:italic>Als2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice are mildly hypoactive. Altered trophic receptor trafficking in neurons of\n                    <jats:italic>Als2<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice may underlie the histopathological and behavioral changes observed and the pathogenesis of ALS2.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0510197103","type":"journal-article","created":{"date-parts":[[2006,6,12]],"date-time":"2006-06-12T21:05:00Z","timestamp":1150146300000},"page":"9595-9600","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":130,"title":["<i>Als2<\/i>\n                    -deficient mice exhibit disturbances in endosome trafficking associated with motor behavioral abnormalities"],"prefix":"10.1073","volume":"103","author":[{"given":"R. S.","family":"Devon","sequence":"first","affiliation":[{"name":"*Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, and Child &amp; Family Research Institute, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. C.","family":"Orban","sequence":"additional","affiliation":[{"name":"*Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, and Child &amp; Family Research Institute, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Gerrow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Brain Research Centre, University of British Columbia, Vancouver, BC, Canada V6T 2A1;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. A.","family":"Barbieri","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Florida International University, Miami, FL 33199;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Schwab","sequence":"additional","affiliation":[{"name":"*Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, and Child &amp; Family Research Institute, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. P.","family":"Cao","sequence":"additional","affiliation":[{"name":"*Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, and Child &amp; Family Research Institute, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. R.","family":"Helm","sequence":"additional","affiliation":[{"name":"*Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, and Child &amp; Family Research Institute, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Bissada","sequence":"additional","affiliation":[{"name":"*Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, and Child &amp; Family Research Institute, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Cruz-Aguado","sequence":"additional","affiliation":[{"name":"*Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, and Child &amp; Family Research Institute, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.-L.","family":"Davidson","sequence":"additional","affiliation":[{"name":"*Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, and Child &amp; Family Research Institute, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Witmer","sequence":"additional","affiliation":[{"name":"*Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, and Child &amp; Family Research Institute, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Metzler","sequence":"additional","affiliation":[{"name":"*Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, and Child &amp; Family Research Institute, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. K.","family":"Lam","sequence":"additional","affiliation":[{"name":"International Collaboration on Repair Discoveries and Department of Zoology, University of British Columbia, Vancouver, BC, Canada V6T 1Z4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Tetzlaff","sequence":"additional","affiliation":[{"name":"International Collaboration on Repair Discoveries and Department of Zoology, University of British Columbia, Vancouver, BC, Canada V6T 1Z4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. M.","family":"Simpson","sequence":"additional","affiliation":[{"name":"*Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, and Child &amp; Family Research Institute, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. M.","family":"McCaffery","sequence":"additional","affiliation":[{"name":"**Integrated Imaging Center, Department of Biology, The Johns Hopkins University, Baltimore, MD 21218; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. E.","family":"El-Husseini","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Brain Research Centre, University of British Columbia, Vancouver, BC, Canada V6T 2A1;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. R.","family":"Leavitt","sequence":"additional","affiliation":[{"name":"*Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, and Child &amp; Family Research Institute, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. R.","family":"Hayden","sequence":"additional","affiliation":[{"name":"*Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, and Child &amp; Family Research Institute, 980 West 28th Avenue, Vancouver, BC, Canada V5Z 4H4;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,6,20]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1001-166"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1001-160"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10422"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/342359"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.2003.00138.x"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2004.10.002"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M313504200"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg184"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410508200"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(98)70018-1"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1261"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90316-Q"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/14075"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200211087"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.12.023"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/35052055"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/2464"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.2001.0443"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)32224-X"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.06.043"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2005.04.011"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1086137"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2004.06.005"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2005.01.010"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(93)90265-D"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.22.12306"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2005.01.010"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2004.07.092"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1645-05.2005"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddi440"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(01)00189-7"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(95)57031-4"},{"key":"e_1_3_4_33_2","unstructured":"C. Panzeri C. De Palma A. Martinuzzi A. Daga G. De Polo N. Bresolin C. C. Miller E. L. Tudor E. Clementi M. T. Bassi Brain 2006)."}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0510197103","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T14:19:56Z","timestamp":1649773196000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0510197103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,6,20]]},"references-count":33,"journal-issue":{"issue":"25","published-print":{"date-parts":[[2006,6,20]]}},"alternative-id":["10.1073\/pnas.0510197103"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0510197103","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,6,20]]},"assertion":[{"value":"2005-11-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-06-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}