{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:28:37Z","timestamp":1790710117028,"version":"4.1.0"},"reference-count":60,"publisher":"National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2013,2,19]]},"abstract":"<jats:p>\n                    Peripheral nervous system abnormalities, including neuropathy, have been reported in people with cystic fibrosis. These abnormalities have largely been attributed to secondary manifestations of the disease. We tested the hypothesis that disruption of the\n                    <jats:italic>cystic fibrosis transmembrane conductance regulator<\/jats:italic>\n                    (\n                    <jats:italic>CFTR<\/jats:italic>\n                    ) gene directly influences nervous system function by studying newborn\n                    <jats:italic>CFTR<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    pigs. We discovered CFTR expression and activity in Schwann cells, and loss of CFTR caused ultrastructural myelin sheath abnormalities similar to those in known neuropathies. Consistent with neuropathic changes, we found increased transcripts for\n                    <jats:italic>myelin protein zero<\/jats:italic>\n                    , a gene that, when mutated, can cause axonal and\/or demyelinating neuropathy. In addition, axon density was reduced and conduction velocities of the trigeminal and sciatic nerves were decreased. Moreover, in vivo auditory brainstem evoked potentials revealed delayed conduction of the vestibulocochlear nerve. Our data suggest that loss of\n                    <jats:italic>CFTR<\/jats:italic>\n                    directly alters Schwann cell function and that some nervous system defects in people with cystic fibrosis are likely primary.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1222729110","type":"journal-article","created":{"date-parts":[[2013,2,4]],"date-time":"2013-02-04T23:29:25Z","timestamp":1360020565000},"page":"3083-3088","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":50,"title":["CFTR-deficient pigs display peripheral nervous system defects at birth"],"prefix":"10.1073","volume":"110","author":[{"given":"Leah R.","family":"Reznikov","sequence":"first","affiliation":[{"name":"Departments of aInternal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Dong","sequence":"additional","affiliation":[{"name":"Pediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeng-Haur","family":"Chen","sequence":"additional","affiliation":[{"name":"Departments of aInternal Medicine,"},{"name":"Howard Hughes Medical Institute, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas O.","family":"Moninger","sequence":"additional","affiliation":[{"name":"Central Microscopy Research Facility, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Min","family":"Park","sequence":"additional","affiliation":[{"name":"Departments of aInternal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhou","family":"Zhang","sequence":"additional","affiliation":[{"name":"Otolaryngology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianyang","family":"Du","sequence":"additional","affiliation":[{"name":"Departments of aInternal Medicine,"},{"name":"Howard Hughes Medical Institute, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S.","family":"Hildebrand","sequence":"additional","affiliation":[{"name":"Otolaryngology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J. H.","family":"Smith","sequence":"additional","affiliation":[{"name":"Otolaryngology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph O.","family":"Randak","sequence":"additional","affiliation":[{"name":"Pediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Stoltz","sequence":"additional","affiliation":[{"name":"Departments of aInternal Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Welsh","sequence":"additional","affiliation":[{"name":"Departments of aInternal Medicine,"},{"name":"Molecular Physiology and Biophysics,"},{"name":"Howard Hughes Medical Institute, University of Iowa Roy J. and Lucille A. Carver College of Medicine, Iowa City, IA 52242"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2013,2,4]]},"reference":[{"key":"e_1_3_3_1_2","unstructured":"MJ Welsh BW Ramsey F Accurso GR Cutting Cystic fibrosis. The Metabolic and Molecular Basis of Inherited Disease eds Scriver CR Beaudet AL Sly WS Valle D Childs B Vogelstein B (McGraw-Hill New York) 8th Ed pp 5121\u20135189. (2001)."},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.1.S3"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra043184"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.WNP.0b013e3181e0a9f9"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02967830"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.4035357"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2006.03.003"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9681(83)90062-0"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198006263022605"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.1996.tb15032.x"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1159\/000116651"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.68.2.187"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2010.09914.x"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/1752-1947-5-366"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.105.021436"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199408150-00035"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1165\/ajrcmb\/8.2.201"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2009.28"},{"key":"e_1_3_3_19_2","first-page":"911","article-title":"Autonomic and airway reactivity in obligate heterozygotes for cystic fibrosis","volume":"129","author":"Davis PB","year":"1984","unstructured":"PB Davis, Autonomic and airway reactivity in obligate heterozygotes for cystic fibrosis. Am Rev Respir Dis 129, 911\u2013914 (1984).","journal-title":"Am Rev Respir Dis"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI34773"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1163600"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3000928"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.200409059"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004019900175"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.50.3.799"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm257"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.46.5.1318"},{"key":"e_1_3_3_28_2","first-page":"39","article-title":"Charcot\u2013Marie\u2013Tooth disease and related genetic neuropathies","volume":"18","author":"Patzko A","year":"2012","unstructured":"A Patzko, ME Shy, Charcot\u2013Marie\u2013Tooth disease and related genetic neuropathies. Continuum (Minneap Minn) 18, 39\u201359 (2012).","journal-title":"Continuum (Minneap Minn)"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22658"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr081"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200402087"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.027128"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.148.5.1021"},{"key":"e_1_3_3_34_2","first-page":"640","article-title":"Alterations of annexin expression in pathological neuronal and glial reactions. Immunohistochemical localization of annexins I, II (p36 and p11 subunits), IV, and VI in the human hippocampus","volume":"145","author":"Eberhard DA","year":"1994","unstructured":"DA Eberhard, MD Brown, SR VandenBerg, Alterations of annexin expression in pathological neuronal and glial reactions. Immunohistochemical localization of annexins I, II (p36 and p11 subunits), IV, and VI in the human hippocampus. Am J Pathol 145, 640\u2013649 (1994).","journal-title":"Am J Pathol"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/62.7.751"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.66.6.779"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/119.3.741"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2011.06.006"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-11-04120.2000"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awg012"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.69.6.806"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(88)80371-8"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2012.05.015"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.67.2.174"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.107201"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0b013e3181ffc317"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1993.sp019872"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2007.06.014"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2007.02.003"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1038\/35013070"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2007.02.002"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1513\/pats.2306015"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.sempedsurg.2009.07.001"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1743-3150.2004.00491.x"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1136\/thx.42.7.538"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1015281107"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2003.10.011"},{"key":"e_1_3_3_58_2","volume-title":"Muscle Biopsy: A Practical Approach","author":"Dubowitz V","year":"2007","unstructured":"V Dubowitz, R Lane, CA Sewry Muscle Biopsy: A Practical Approach (Saunders Elsevier, 3rd Ed, Philadelphia, 2007).","edition":"3"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2009.12.006"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1093\/beheco\/arn020"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1222729110","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T21:42:16Z","timestamp":1649799736000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1222729110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2,4]]},"references-count":60,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2013,2,19]]}},"alternative-id":["10.1073\/pnas.1222729110"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1222729110","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,4]]},"assertion":[{"value":"2013-02-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}