{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:41:32Z","timestamp":1790052092269,"version":"4.0.1"},"reference-count":99,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,9,25]],"date-time":"2017-09-25T00:00:00Z","timestamp":1506297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P24843\u2010B24"],"award-info":[{"award-number":["P24843\u2010B24"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["I2738\u2010B26"],"award-info":[{"award-number":["I2738\u2010B26"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P24685\u2010B24"],"award-info":[{"award-number":["P24685\u2010B24"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Inherited deficiency in ether lipids, a subgroup of phospholipids whose biosynthesis needs peroxisomes, causes the fatal human disorder rhizomelic chondrodysplasia punctata. The exact roles of ether lipids in the mammalian organism and, therefore, the molecular mechanisms underlying the disease are still largely enigmatic. Here, we used <jats:italic>glyceronephosphate O\u2010acyltransferase<\/jats:italic> knockout (<jats:italic>Gnpat<\/jats:italic> KO) mice to study the consequences of complete inactivation of ether lipid biosynthesis and documented substantial deficits in motor performance and muscle strength of these mice. We hypothesized that, probably in addition to previously described cerebellar abnormalities and myelination defects in the peripheral nervous system, an impairment of neuromuscular transmission contributes to the compromised motor abilities. Structurally, a morphologic examination of the neuromuscular junction (NMJ) in diaphragm muscle at different developmental stages revealed aberrant axonal branching and a strongly increased area of nerve innervation in <jats:italic>Gnpat<\/jats:italic> KO mice. Post\u2010synaptically, acetylcholine receptor (AChR) clusters colocalized with nerve terminals within a widened endplate zone. In addition, we detected atypical AChR clustering, as indicated by decreased size and number of clusters following stimulation with agrin, <jats:italic>in\u00a0vitro<\/jats:italic>. The turnover of AChRs was unaffected in ether lipid\u2010deficient mice. Electrophysiological evaluation of the adult diaphragm indicated that although evoked potentials were unaltered in <jats:italic>Gnpat<\/jats:italic> KO mice, ether lipid deficiency leads to fewer spontaneous synaptic vesicle fusion events but, conversely, an increased post\u2010synaptic response to spontaneous vesicle exocytosis. We conclude from our findings that ether lipids are essential for proper development and function of the NMJ and may, therefore, contribute to motor performance.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14082-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p><jats:bold>Read the Editorial Highlight for this article on page<\/jats:bold> <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/doi.org\/10.1111\/jnc.14156\">463<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14082","type":"journal-article","created":{"date-parts":[[2017,5,29]],"date-time":"2017-05-29T06:06:50Z","timestamp":1496038010000},"page":"569-583","source":"Crossref","is-referenced-by-count":44,"title":["Reduced muscle strength in ether lipid\u2010deficient mice is accompanied by altered development and function of the neuromuscular junction"],"prefix":"10.1111","volume":"143","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0852-1524","authenticated-orcid":false,"given":"Fabian","family":"Dorninger","sequence":"first","affiliation":[{"name":"Department of Pathobiology of the Nervous System Center for Brain Research Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Herbst","sequence":"additional","affiliation":[{"name":"Section\u00a0for Synapse Formation Center for Brain Research Medical University of Vienna Vienna Austria"},{"name":"Center for Pathophysiology Infectiology and Immunology Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bojana","family":"Kravic","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry Friedrich\u2010Alexander University of Erlangen\u2010Nuremberg Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahar Z.","family":"Camurdanoglu","sequence":"additional","affiliation":[{"name":"Section\u00a0for Synapse Formation Center for Brain Research Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Macinkovic","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry Friedrich\u2010Alexander University of Erlangen\u2010Nuremberg Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Zeitler","sequence":"additional","affiliation":[{"name":"Department of Pathobiology of the Nervous System Center for Brain Research Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Forss\u2010Petter","sequence":"additional","affiliation":[{"name":"Department of Pathobiology of the Nervous System Center for Brain Research Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siegfried","family":"Strack","sequence":"additional","affiliation":[{"name":"Institute of Toxicology and Genetics Karlsruhe Institute of Technology Eggenstein\u2010Leopoldshafen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muzamil Majid","family":"Khan","sequence":"additional","affiliation":[{"name":"Institute of Toxicology and Genetics Karlsruhe Institute of Technology Eggenstein\u2010Leopoldshafen Germany"},{"name":"Institute of Molecular and Cell Biology Faculty of Biotechnology University of Applied Sciences Mannheim Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans R.","family":"Waterham","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases Academic Medical Center University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00fcdiger","family":"Rudolf","sequence":"additional","affiliation":[{"name":"Institute of Toxicology and Genetics Karlsruhe Institute of Technology Eggenstein\u2010Leopoldshafen Germany"},{"name":"Institute of Molecular and Cell Biology Faculty of Biotechnology University of Applied Sciences Mannheim Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Said","family":"Hashemolhosseini","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry Friedrich\u2010Alexander University of Erlangen\u2010Nuremberg Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Pathobiology of the Nervous System Center for Brain Research Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,9,25]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1004956107"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80303-7"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1733-14.2014"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(99)01501-X"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2015.12.005"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1074"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2012.05.008"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds097"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2011.01.002"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90189-J"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2005.11.019"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep33583"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142301.ns0812s15"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200607083"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00711431"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2010.06.008"},{"key":"e_1_2_7_18_1","first-page":"e2610","article-title":"Measuring the strength of mice","volume":"76","author":"Deacon R. M.","year":"2013","journal-title":"J. Vis. Exp."},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-08-03023.1999"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2014.11.005"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-007-0288-4"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2011.00119"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2245"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1177\/107385840100700308"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1001695107"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.10.3479"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.53.3.265"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01870004"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81253-2"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00185a019"},{"key":"e_1_2_7_31_1","doi-asserted-by":"crossref","first-page":"4170","DOI":"10.1523\/JNEUROSCI.17-11-04170.1997","article-title":"Slow\u2010channel transgenic mice: a model of postsynaptic organellar degeneration at the neuromuscular junction","volume":"17","author":"Gomez C. M.","year":"1997","journal-title":"J. Neurosci."},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.P700023-JLR200"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2006.08.038"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0006261"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.2174\/1567205052772786"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2014.08.026"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.1.67"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00112"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(89)90510-5"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(85)90142-6"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2008.05.018"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-654150-2.50016-6"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.12.5096"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0904762106"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M021204"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1957.sp005811"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2007.04977.x"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.2144\/05381BM03"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1056594"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.10.002"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-009-0809-7"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-011-0836-9"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13710"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(03)00147-1"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.2001.0997"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1105996108"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn2053"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.22.13461"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-3084(96)02580-7"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-10-03663.2000"},{"key":"e_1_2_7_61_1","first-page":"2626","article-title":"Skeletal muscle lipids. II. Nonutilization of intracellular lipid esters as an energy source for contractile activity","volume":"241","author":"Masoro E. J.","year":"1966","journal-title":"J. Biol. Chem."},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)01020-6"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(00)02205-8"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt053"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-3084(94)90054-X"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2008.03.020"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2010.10.054"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj20031672"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.E600002-JLR200"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi0156557"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1992.sp019429"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.69.1.419"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg191"},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0914087107"},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1608"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)30187-5"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0101076"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.276.5312.599"},{"key":"e_1_2_7_79_1","doi-asserted-by":"publisher","DOI":"10.1038\/35097557"},{"key":"e_1_2_7_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.01.012"},{"key":"e_1_2_7_81_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2012.04.005"},{"key":"e_1_2_7_82_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI72063"},{"key":"e_1_2_7_83_1","doi-asserted-by":"publisher","DOI":"10.1038\/42408"},{"key":"e_1_2_7_84_1","doi-asserted-by":"publisher","DOI":"10.1038\/35036052"},{"key":"e_1_2_7_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2006.09.010"},{"key":"e_1_2_7_86_1","doi-asserted-by":"publisher","DOI":"10.1385\/JMN:30:1:37"},{"key":"e_1_2_7_87_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020524"},{"key":"e_1_2_7_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.10.030"},{"key":"e_1_2_7_89_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp110"},{"key":"e_1_2_7_90_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.2.127"},{"key":"e_1_2_7_91_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90089-V"},{"key":"e_1_2_7_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00688-8"},{"key":"e_1_2_7_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemphyslip.2011.06.008"},{"key":"e_1_2_7_94_1","doi-asserted-by":"publisher","DOI":"10.2217\/clp.10.16"},{"key":"e_1_2_7_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2006.08.010"},{"key":"e_1_2_7_96_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn783"},{"key":"e_1_2_7_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.10.006"},{"key":"e_1_2_7_98_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2807-05.2006"},{"key":"e_1_2_7_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)38000-1"},{"key":"e_1_2_7_100_1","doi-asserted-by":"publisher","DOI":"10.1042\/bj3380769"}],"container-title":["Journal of Neurochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjnc.14082","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jnc.14082","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T19:12:00Z","timestamp":1695755520000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jnc.14082"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,25]]},"references-count":99,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2017,12]]}},"alternative-id":["10.1111\/jnc.14082"],"URL":"https:\/\/doi.org\/10.1111\/jnc.14082","archive":["Portico"],"relation":{},"ISSN":["0022-3042","1471-4159"],"issn-type":[{"value":"0022-3042","type":"print"},{"value":"1471-4159","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,25]]}}}