{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T21:47:38Z","timestamp":1762897658251,"version":"build-2065373602"},"reference-count":44,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2000,7,24]],"date-time":"2000-07-24T00:00:00Z","timestamp":964396800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2000,9]]},"abstract":"<jats:p>Human familial neurohypophyseal diabetes insipidus (FNDI) is an autosomal dominant endocrine disorder that presents in early childhood as excessive drinking and urination as a consequence of a progressive loss of secretion of vasopressin (VP) from posterior pituitary nerve terminals. Mutations in the VP gene have been implicated as the cause of FNDI, but the mechanisms by which these mutants manifest their pathology, and prevent the secretion of the co\u2010expressed wild\u2010type protein, are unknown. One hypothesis suggests that mutant precursors are toxic, and stop the synthesis of wild\u2010type VP by killing expressing cells. Another hypothesis suggests that aberrant interactions between mutant and wild\u2010type precursors might directly inhibit the elaboration or secretion of the products of the normal allele. We have tested these hypotheses using new animal models\u2010\u2010transgenic rats that express an FNDI mutant VP gene that encodes a truncated precursor (Cys67stop). Cell\u2010specific and inducible expression of the Cys67stop mutation in rat VP hypothalamic neurons does not result in cell death or atrophy. Rather, expression of the FNDI mutant causes a neuronal pathology characterized by distorted structures in the cell body that are labeled by antisera that recognize endoplasmic reticulum (ER) markers, and that accumulate both mutant and wild\u2010type VP gene products. This is accompanied by an increase in the abundance of the mannose\u20106\u2010phosphate receptor (MPR), a marker of endosome\u2010lysosome activity. We suggest that FNDI in humans may be initiated, as in our transgenic rat model, by the trapping of wild\u2010type VP gene products within an ER, which is targeted for lysosomal degradation by autophagy.<\/jats:p>","DOI":"10.1096\/fj.99-0892fje","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T19:03:10Z","timestamp":1027710190000},"page":"1680-1684","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Endoplasmic reticulum derangement in hypothalamic neurons of rats expressing a familial neurohypophyseal diabetes insipidus mutant vasopressin transgene"],"prefix":"10.1096","volume":"14","author":[{"given":"S-L.","family":"Si-Hoe","sequence":"first","affiliation":[{"name":"University of Bristol U.K."},{"name":"Institute of Molecular and Cell Biology Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.M.","family":"de Bree","sequence":"additional","affiliation":[{"name":"University of Bristol U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Nijenhuis","sequence":"additional","affiliation":[{"name":"Rudolf Magnus Institute for Neuroscience Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.E.","family":"Davies","sequence":"additional","affiliation":[{"name":"University of Bristol U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.M.C.","family":"Howell","sequence":"additional","affiliation":[{"name":"University of Bristol U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Tinley","sequence":"additional","affiliation":[{"name":"University of Bristol U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.J.","family":"Waller","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Biology Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Q.","family":"Zeng","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Biology Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.","family":"Zalm","sequence":"additional","affiliation":[{"name":"Rudolf Magnus Institute for Neuroscience Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Sonnemans","sequence":"additional","affiliation":[{"name":"Netherlands Institute for Brain Research Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F.W.","family":"Van Leeuwen","sequence":"additional","affiliation":[{"name":"Netherlands Institute for Brain Research Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.P.H.","family":"Burbach","sequence":"additional","affiliation":[{"name":"Rudolf Magnus Institute for Neuroscience Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Murphy","sequence":"additional","affiliation":[{"name":"University of Bristol U.K."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2000,7,24]]},"reference":[{"volume-title":"Vasopressin","year":"1985","author":"Schrier R.W.","key":"e_1_2_6_2_1"},{"key":"e_1_2_6_3_1","first-page":"311","volume-title":"Williams Textbook of Endocrinology","author":"Reeves W.B.","year":"1992"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6153132"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/pgmj.57.663.36"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.80.4.1352"},{"key":"e_1_2_6_7_1","first-page":"107","article-title":"Identification of 13 new mutations in the vasopressin-neurophysin II gene in 17 kindreds with familial autosomal dominant neurohypophyseal diabetes insipidus","volume":"58","author":"Rittig S.","year":"1996","journal-title":"Am. 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