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To achieve this objective, wild\u2010type (WT) protein and the amyloidogenic variants F57I and D67H were expressed in\n                    <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    using the\n                    <jats:italic>UAS\u2010gal4<\/jats:italic>\n                    system and both the ubiquitous and retinal expression drivers\n                    <jats:italic>Act5C\u2010gal4<\/jats:italic>\n                    and\n                    <jats:italic>gmr\u2010gal4<\/jats:italic>\n                    . The nontransgenic\n                    <jats:italic>\n                      w\n                      <jats:sup>1118<\/jats:sup>\n                      Drosophila\n                    <\/jats:italic>\n                    line was used as a control throughout. We utilized ELISA experiments to probe lysozyme protein levels, scanning electron microscopy for eye phenotype classification, and immunohistochemistry to detect the unfolded protein response (UPR) activation. We observed that expressing the destabilized F57I and D67H lysozymes triggers UPR activation, resulting in degradation of these variants, whereas the WT lysozyme is secreted into the fly hemolymph. Indeed, the level of WT was up to 17 times more abundant than the variant proteins. In addition, the F57I variant gave rise to a significant disruption of the eye development, and this correlated to pronounced UPR activation. These results support the concept that the onset of familial amyloid disease is linked to an inability of the UPR to degrade completely the amyloidogenic lysozymes prior to secretion, resulting in secretion of these destabilized variants, thereby leading to deposition and associated organ damage.\u2014Kumita, J. R., Helmfors, L., Williams, J., Luheshi, L. M., Menzer, L., Dumoulin, M., Lomas, D. A., Crowther, D. C., Dobson, C. M., Brorsson, A.\u2010C. Disease\u2010related amyloidogenic variants of human lysozyme trigger the unfolded protein response and disturb eye development in\n                    <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    .\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    26, 192\u2010202 (2012).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.11-185983","type":"journal-article","created":{"date-parts":[[2011,9,30]],"date-time":"2011-09-30T07:18:30Z","timestamp":1317367110000},"page":"192-202","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Disease\u2010related amyloidogenic variants of human lysozyme trigger the unfolded protein response and disturb eye development in\n                    <i>Drosophila melanogaster<\/i>"],"prefix":"10.1096","volume":"26","author":[{"given":"Janet R.","family":"Kumita","sequence":"first","affiliation":[{"name":"Department of Chemistry University of Cambridge  Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Helmfors","sequence":"additional","affiliation":[{"name":"Division of Molecular Biotechnology, Department of Physics Chemistry and Biology, Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jocy","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Biochemistry University of Cambridge  Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leila M.","family":"Luheshi","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Cambridge  Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Menzer","sequence":"additional","affiliation":[{"name":"Laboratory of Enzymology and Protein Folding, Centre of Protein Engineering Institute of Chemistry B6c, University of Lie'ge  Lie'ge Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mireille","family":"Dumoulin","sequence":"additional","affiliation":[{"name":"Laboratory of Enzymology and Protein Folding, Centre of Protein Engineering Institute of Chemistry B6c, University of Lie'ge  Lie'ge Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Lomas","sequence":"additional","affiliation":[{"name":"Cambridge Institute for Medical Research  Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Damian C.","family":"Crowther","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Cambridge  Cambridge UK"},{"name":"Cambridge Institute for Medical Research  Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher M.","family":"Dobson","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Cambridge  Cambridge UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann\u2010Christin","family":"Brorsson","sequence":"additional","affiliation":[{"name":"Division of Molecular Biotechnology, Department of Physics Chemistry and Biology, Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2011,9,29]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.1922.0023"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/362553a0"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/385787a0"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2002.00205.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2003.00904.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1002\/humu.9393","article-title":"ALys amyloidosis caused by compound heterozygosity in exon 2 (Thr70Asn) and Exon 4 (Trp112Arg) of the lysozyme gene","volume":"27","author":"R\u00f6cken C.","year":"2005","journal-title":"Hum. 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