{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:20:40Z","timestamp":1791494440695,"version":"4.3.4"},"reference-count":134,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"748","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2024,5,22]]},"abstract":"<jats:p>\n            Blood-CNS barrier disruption is a hallmark of numerous neurological disorders, yet whether barrier breakdown is sufficient to trigger neurodegenerative disease remains unresolved. Therapeutic strategies to mitigate barrier hyperpermeability are also limited. Dominant missense mutations of the cation channel transient receptor potential vanilloid 4 (TRPV4) cause forms of hereditary motor neuron disease. To gain insights into the cellular basis of these disorders, we generated knock-in mouse models of TRPV4 channelopathy by introducing two disease-causing mutations (R269C and R232C) into the endogenous mouse\n            <jats:italic>Trpv4<\/jats:italic>\n            gene. TRPV4 mutant mice exhibited weakness, early lethality, and regional motor neuron loss. Genetic deletion of the mutant\n            <jats:italic>Trpv4<\/jats:italic>\n            allele from endothelial cells (but not neurons, glia, or muscle) rescued these phenotypes. Symptomatic mutant mice exhibited focal disruptions of blood\u2013spinal cord barrier (BSCB) integrity, associated with a gain of function of mutant TRPV4 channel activity in neural vascular endothelial cells (NVECs) and alterations of NVEC tight junction structure. Systemic administration of a TRPV4-specific antagonist abrogated channel-mediated BSCB impairments and provided a marked phenotypic rescue of symptomatic mutant mice. Together, our findings show that mutant TRPV4 channels can drive motor neuron degeneration in a non\u2013cell autonomous manner by precipitating focal breakdown of the BSCB. Further, these data highlight the reversibility of TRPV4-mediated BSCB impairments and identify a potential therapeutic strategy for patients with TRPV4 mutations.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adk1358","type":"journal-article","created":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T17:58:30Z","timestamp":1716400710000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":29,"title":["Gain-of-function mutations of TRPV4 acting in endothelial cells drive blood-CNS barrier breakdown and motor neuron degeneration in mice"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2082-0191","authenticated-orcid":true,"given":"Jeremy M.","family":"Sullivan","sequence":"first","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8469-0154","authenticated-orcid":true,"given":"Anna M.","family":"Bagnell","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7279-5779","authenticated-orcid":true,"given":"Jonathan","family":"Alevy","sequence":"additional","affiliation":[{"name":"Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvia Mena","family":"Avila","sequence":"additional","affiliation":[{"name":"George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI 02881, USA."},{"name":"Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ljubica","family":"Mihaljevi\u0107","sequence":"additional","affiliation":[{"name":"Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela C.","family":"Saavedra-Rivera","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6266-9741","authenticated-orcid":true,"given":"Lingling","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer S.","family":"Huh","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6581-9728","authenticated-orcid":true,"given":"Brett A.","family":"McCray","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8715-1439","authenticated-orcid":true,"given":"William H.","family":"Aisenberg","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0252-9760","authenticated-orcid":true,"given":"Aamir R.","family":"Zuberi","sequence":"additional","affiliation":[{"name":"Jackson Laboratory, Bar Harbor, ME 04609, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7015-6631","authenticated-orcid":true,"given":"Laurent","family":"Bogdanik","sequence":"additional","affiliation":[{"name":"Jackson Laboratory, Bar Harbor, ME 04609, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathleen M.","family":"Lutz","sequence":"additional","affiliation":[{"name":"Jackson Laboratory, Bar Harbor, ME 04609, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9122-6077","authenticated-orcid":true,"given":"Zhaozhu","family":"Qiu","sequence":"additional","affiliation":[{"name":"Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6177-4849","authenticated-orcid":true,"given":"Katharina A.","family":"Quinlan","sequence":"additional","affiliation":[{"name":"George and Anne Ryan Institute for Neuroscience, University of Rhode Island, Kingston, RI 02881, USA."},{"name":"Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5417-0828","authenticated-orcid":true,"given":"Peter C.","family":"Searson","sequence":"additional","affiliation":[{"name":"Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD 21218, USA."},{"name":"Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA."},{"name":"Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5088-6012","authenticated-orcid":true,"given":"Charlotte J.","family":"Sumner","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."},{"name":"Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0234-x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1815-1"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190062"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1642-11.2011"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.512"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.509"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.508"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181ffe4bb"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2011.12.003"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq109"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000450"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-011-5947-7"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00016.2015"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39345-0"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000029"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21699-y"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39346-z"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.237685"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31820f2de3"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-012-0328-7"},{"key":"e_1_3_2_22_2","doi-asserted-by":"crossref","first-page":"e0152833","DOI":"10.1371\/journal.pone.0152833","article-title":"Critical endothelial regulation by LRP5 during retinal vascular development","volume":"11","author":"Huang W.","year":"2016","unstructured":"W. Huang, Q. Li, M. Amiry-Moghaddam, M. Hokama, S. H. Sardi, M. Nagao, M. L. Warman, B. R. Olsen, Critical endothelial regulation by LRP5 during retinal vascular development. PLOS ONE 11, e0152833 (2016).","journal-title":"PLOS ONE"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature25739"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0590-4"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.36187"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-019-0497-x"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.01.015"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.113392"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.38689"},{"key":"e_1_3_2_30_2","doi-asserted-by":"crossref","unstructured":"A. K. Thron Vascular Anatomy of the Spinal Cord (Springer-Verlag 2016).","DOI":"10.1007\/978-3-319-27440-9"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004276"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.10.042"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1113\/JP275052"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14072"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.03.003"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.01.014"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-018-0232-x"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00050.2017"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2023.03.005"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.145789"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3966"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI161507"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.01.007"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04521-7"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04369-3"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abi7377"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-023-01334-3"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.11.077"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.123.319516"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15687"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00914"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10523"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1111\/apha.12860"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01511-z"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1813217115"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.45542"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1907467117"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn2073"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2022.114084"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.13.4879"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2014.01.026"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-021-02091-1"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.2337\/db21-0711"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.14816"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2020.113244"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2007.12.052"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.149.5.1157"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-6-74"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2019.10.018"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2012.05.056"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1401595111"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-012-1039-8"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20202207"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1038\/s44161-021-00014-4"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2247-3"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.188"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1710329115"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2018.00097"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2035-19.2020"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b21-00512"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1183\/23120541.00269-2021"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40256-018-00320-6"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.1809"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.120.000307"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1002\/bies.202100288"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-43254-y"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbiomolbio.2009.10.002"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31766"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2008.08.002"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01070.2011"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-020-01444-9"},{"key":"e_1_3_2_92_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abb6871"},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2012.219"},{"key":"e_1_3_2_94_2","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51523"},{"key":"e_1_3_2_95_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25780"},{"key":"e_1_3_2_96_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI128152"},{"key":"e_1_3_2_97_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI76431"},{"key":"e_1_3_2_98_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0027385"},{"key":"e_1_3_2_99_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.2003586"},{"key":"e_1_3_2_100_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2010.05436.x"},{"key":"e_1_3_2_101_2","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X20941449"},{"key":"e_1_3_2_102_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI124120"},{"key":"e_1_3_2_103_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2022.101826"},{"key":"e_1_3_2_104_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.51276"},{"key":"e_1_3_2_105_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00019.2017"},{"key":"e_1_3_2_106_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2020.127022"},{"key":"e_1_3_2_107_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aav9739"},{"key":"e_1_3_2_108_2","doi-asserted-by":"publisher","DOI":"10.1002\/biot.201100189"},{"key":"e_1_3_2_109_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.862101"},{"key":"e_1_3_2_110_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0333-8"},{"key":"e_1_3_2_111_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08000"},{"key":"e_1_3_2_112_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature25448"},{"key":"e_1_3_2_113_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-15-06309.2002"},{"key":"e_1_3_2_114_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0527-y"},{"key":"e_1_3_2_115_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature12176"},{"key":"e_1_3_2_116_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2681-2"},{"key":"e_1_3_2_117_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature07619"},{"key":"e_1_3_2_118_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-02-555151"},{"key":"e_1_3_2_119_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-018-0020-z"},{"key":"e_1_3_2_120_2","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.2000.0106"},{"key":"e_1_3_2_121_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1251487"},{"key":"e_1_3_2_122_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature21724"},{"key":"e_1_3_2_123_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/27.19.e27"},{"key":"e_1_3_2_124_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat3987"},{"key":"e_1_3_2_125_2","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20474"},{"key":"e_1_3_2_126_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.102650499"},{"key":"e_1_3_2_127_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aal1669"},{"key":"e_1_3_2_128_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008942828960"},{"key":"e_1_3_2_129_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2625-x"},{"key":"e_1_3_2_130_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn1340"},{"key":"e_1_3_2_131_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2388-4"},{"key":"e_1_3_2_132_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1095"},{"key":"e_1_3_2_133_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature11007"},{"key":"e_1_3_2_134_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf6803"},{"key":"e_1_3_2_135_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.258203"}],"container-title":["Science Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/scitranslmed.adk1358","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T17:59:04Z","timestamp":1716400744000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/scitranslmed.adk1358"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,22]]},"references-count":134,"journal-issue":{"issue":"748","published-print":{"date-parts":[[2024,5,22]]}},"alternative-id":["10.1126\/scitranslmed.adk1358"],"URL":"https:\/\/doi.org\/10.1126\/scitranslmed.adk1358","relation":{},"ISSN":["1946-6234","1946-6242"],"issn-type":[{"value":"1946-6234","type":"print"},{"value":"1946-6242","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,22]]},"assertion":[{"value":"2023-08-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eadk1358"}}