{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T10:42:24Z","timestamp":1768646544440,"version":"3.49.0"},"reference-count":26,"publisher":"The Company of Biologists","issue":"3","license":[{"start":{"date-parts":[[1989,3,1]],"date-time":"1989-03-01T00:00:00Z","timestamp":604713600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1989,3,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Genetic ablation techniques were used to study the role of the lens in mammalian eye development. Ablation was accomplished by microinjecting murine eggs with chimeric DNA constructs in which the aA-crystallin gene regulatory sequence (\u2212366 to +46) was fused to the highly cytotoxic diphtheria toxin gene coding sequence. For genetic ablation to be successful the promoter regulating expression should be specific and completely silent in cells necessary for normal mouse development. In this report, we describe the generation and analysis of transgenic mice with this readily discernible phenotype: aphakia or eyes without lens. Of the 109 live-born pups, eight carried the transgene and could be grouped according to the apparent severity of eye malformations. Lines 4, 5 and 6 founder (F0) mice had the most severe phenotype. Histological analysis revealed: marked reduction in eye size, total absence of lens, increased retinal cell density and extensive whorling of the retinal fibre layers. The line 1 F0 mouse displayed a distinct lens opacity and lines 2, 3 and 8 F0 mice were mosaics with a relatively mild, but most unusual phenotype. Their eyes contained a small, highly vacuolated lens. The progeny of these mosaics that inherited the transgene, however, again exhibited the severe phenotype. The aberrant structures of the eyes in which complete genetic ablation of the lens has been achieved suggest that the lens plays a pivotal role in the development of multiple components of the murine eye.<\/jats:p>","DOI":"10.1242\/dev.105.3.613","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T00:39:43Z","timestamp":1619397583000},"page":"613-619","source":"Crossref","is-referenced-by-count":40,"title":["Targeted ablation of <i>\u03b1<\/i>-crystalIin-synthesizing cells produces lens-deficient eyes in transgenic mice"],"prefix":"10.1242","volume":"105","author":[{"given":"Satbir","family":"Kaur","sequence":"first","affiliation":[{"name":"Division of Basic Science Research and Department of Pediatrics, Children\u2019s Hospital Research Foundation and University of Cincinnati College of Medicine, Eiland and Bethesda Avenues, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Key","sequence":"additional","affiliation":[{"name":"Division of Basic Science Research and Department of Pediatrics, Children\u2019s Hospital Research Foundation and University of Cincinnati College of Medicine, Eiland and Bethesda Avenues, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Stock","sequence":"additional","affiliation":[{"name":"Division of Basic Science Research and Department of Pediatrics, Children\u2019s Hospital Research Foundation and University of Cincinnati College of Medicine, Eiland and Bethesda Avenues, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John D.","family":"McNeish","sequence":"additional","affiliation":[{"name":"Division of Basic Science Research and Department of Pediatrics, Children\u2019s Hospital Research Foundation and University of Cincinnati College of Medicine, Eiland and Bethesda Avenues, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Akeson","sequence":"additional","affiliation":[{"name":"Division of Basic Science Research and Department of Pediatrics, Children\u2019s Hospital Research Foundation and University of Cincinnati College of Medicine, Eiland and Bethesda Avenues, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. Steven","family":"Potter","sequence":"additional","affiliation":[{"name":"Division of Basic Science Research and Department of Pediatrics, Children\u2019s Hospital Research Foundation and University of Cincinnati College of Medicine, Eiland and Bethesda Avenues, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[1989,3,1]]},"reference":[{"key":"2023050311215527100_DEVELOP_105_3_613C1","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1101\/gad.2.4.453","article-title":"Dwarf mice produced by genetic ablation of growth hormone expressing cells","volume":"2","author":"Behringer","year":"1988","journal-title":"Genes & Dev"},{"key":"2023050311215527100_DEVELOP_105_3_613C2","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1126\/science.3685993","article-title":"Genetic ablation: Targeted ablation of a toxin gene causes microphthalmia in transgenic mice","volume":"238","author":"Breitman","year":"1987","journal-title":"Science"},{"key":"2023050311215527100_DEVELOP_105_3_613C3","doi-asserted-by":"publisher","first-page":"2334","DOI":"10.1073\/pnas.82.8.2334","article-title":"Lens specific expression of chloramphenicol acetyltransferase gene promoted by 5\u2019 flanking sequences of the murine oA-crystallin gene in explanted chicken lens epithelia","volume":"82","author":"Chepelinsky","year":"1985","journal-title":"Proc. natn. Acad. Sci. U.S.A"},{"key":"2023050311215527100_DEVELOP_105_3_613C4","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1128\/br.39.1.54-85.1975","article-title":"Diphtheria toxin: mode of action and structure","volume":"39","author":"Collier","year":"1975","journal-title":"Bacterial. Rev"},{"key":"2023050311215527100_DEVELOP_105_3_613C5","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1002\/jez.1401560104","article-title":"Lens development. I. Role of the lens in eye growth","volume":"156","author":"Coulombre","year":"1964","journal-title":"J. exp. Zool"},{"key":"2023050311215527100_DEVELOP_105_3_613C6","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/0003-2697(83)90418-9","article-title":"Radiolabelling DNA fragments","volume":"132","author":"Feinberg","year":"1983","journal-title":"Anal. 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Top. devl Biol"},{"key":"2023050311215527100_DEVELOP_105_3_613C10","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1101\/gad.2.9.1168","article-title":"Lensspecific expression of recombinant ricin induces developmental defects in the eyes of transgenic mice","volume":"2","author":"Landel","year":"1988","journal-title":"Genes and Dev"},{"key":"2023050311215527100_DEVELOP_105_3_613C11","doi-asserted-by":"publisher","first-page":"1622","DOI":"10.1126\/science.3029873","article-title":"Oncogenesis of the lens in transgenic mice","volume":"235","author":"Mahon","year":"1987","journal-title":"Science"},{"key":"2023050311215527100_DEVELOP_105_3_613C12","first-page":"4660","article-title":"Regulated expression of a diphtheria toxin A-chain gene transfected into human cells: possible strategy for inducing cancer cell suicide","volume":"46","author":"Maxwell","year":"1986","journal-title":"Cancer Res"},{"key":"2023050311215527100_DEVELOP_105_3_613C13","first-page":"7","volume-title":"In Mechanisms of Cataract Formation in the Human Lens","author":"McAvoy","year":"1981"},{"key":"2023050311215527100_DEVELOP_105_3_613C14","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1038\/313600a0","article-title":"Specific expression of an elastase-human growth hormone fusion gene in pancreatic acinar cells of transgenic mice","volume":"313","author":"Orntiz","year":"1985","journal-title":"Nature, Lond"},{"key":"2023050311215527100_DEVELOP_105_3_613C15","doi-asserted-by":"publisher","first-page":"7815","DOI":"10.1073\/pnas.82.23.7815","article-title":"Lens specific expression and developmental regulation of the bacterial chloramphenicol acetyltransferase gene driven by the murine oA-crystallin promoter in transgenic mice","volume":"82","author":"Overbeek","year":"1985","journal-title":"Proc. natn. 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A review of cellular and molecular features","volume":"19","author":"Piatigorsky","year":"1981","journal-title":"Differentiation"},{"key":"2023050311215527100_DEVELOP_105_3_613C19","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1016\/0165-3806(82)90013-X","article-title":"The loss of ganglion cells in the developing retina of the rat","volume":"3","author":"Potts","year":"1982","journal-title":"Dev. Brain Res"},{"key":"2023050311215527100_DEVELOP_105_3_613C20","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/S0070-2153(08)60622-5","article-title":"Cell lineage analysis in mammalian embryogenesis","volume":"23","author":"Rossant","year":"1987","journal-title":"Curr. 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