{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:21:54Z","timestamp":1793330514878,"version":"4.5.0"},"reference-count":33,"publisher":"The Company of Biologists","issue":"11","license":[{"start":{"date-parts":[[2000,6,1]],"date-time":"2000-06-01T00:00:00Z","timestamp":959817600000},"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":[[2000,6,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Analysis of several mutations in the mouse is providing useful insights into the nature of the genes required for the establishment of the left-right axis during early development. Here we describe a new targeted allele of the mouse Tg737 gene, Tg737\u03942-3\u03b1Gal, which causes defects in left-right asymmetry and other abnormalities during embryogenesis. The Tg737 gene was originally identified based on its association with the mouse Oak Ridge Polycystic Kidney (orpk) insertional mutation, which causes polycystic kidney disease and other defects. Complementation tests between the original orpk mutation and the new targeted knock-out mutation demonstrate that Tg737\u03942-3\u03b1Gal behaves as an allele of Tg737. The differences in the phenotype between the two mutations suggest that the orpk mutation is a hypomorphic allele of the Tg737 gene. Unlike the orpk allele, where all homozygotes survive to birth, embryos homozygous for the Tg737\u03942-3\u03b1Gal mutation arrest in development at mid-gestation and exhibit neural tube defects, enlargement of the pericardial sac and, most notably, left-right asymmetry defects. At mid-gestation the direction of heart looping is randomized, and at earlier stages in development lefty-2 and nodal, which are normally expressed asymmetrically, exhibit symmetrical expression in the mutant embryos. Additionally, we determined that the ventral node cells in mutant embryos fail to express the central cilium, which is a characteristic and potentially functional feature of these cells. The expression of both Shh and Hnf3\u03b1 is downregulated in the midline at E8.0, indicating that there are significant alterations in midline development in the Tg737\u03942-3\u03b1Gal homozygous embryos. We propose that the failure of ventral node cells to fully mature alters their ability to undergo differentiation as they migrate out of the node to contribute to the developing midline structures. Analysis of this new knockout allele allows us to define a critical role for the Tg737 gene during early embryogenesis. We have named the product of the Tg737 gene Polaris, which is based on the various polarity related defects associated with the different alleles of the Tg737 gene.<\/jats:p>","DOI":"10.1242\/dev.127.11.2347","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T00:04:16Z","timestamp":1619395456000},"page":"2347-2355","source":"Crossref","is-referenced-by-count":373,"title":["The\n                    <i>Oak Ridge Polycystic Kidney<\/i>\n                    (\n                    <i>orpk<\/i>\n                    ) disease gene is required for left-right axis determination"],"prefix":"10.1242","volume":"127","author":[{"given":"Noel S.","family":"Murcia","sequence":"first","affiliation":[{"name":"Case Western Reserve University 1 Department of Pediatrics, Rainbow Babies and Children\u2019s Hospital , , Cleveland, OH 44106, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William G.","family":"Richards","sequence":"additional","affiliation":[{"name":"2 Neuroscience Department, Amgen, Thousand Oaks, CA 91320, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley K.","family":"Yoder","sequence":"additional","affiliation":[{"name":"University of Alabama at Birmingham 3 Department of Cell Biology , , Birmingham, AL 35294, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael L.","family":"Mucenski","sequence":"additional","affiliation":[{"name":"4 Division of Pulmonary Biology, Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Dunlap","sequence":"additional","affiliation":[{"name":"The University of Tennessee 5 The Program in Microscopy , , Knoxville, TN 37996, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard P.","family":"Woychik","sequence":"additional","affiliation":[{"name":"Case Western Reserve University 1 Department of Pediatrics, Rainbow Babies and Children\u2019s Hospital , , Cleveland, OH 44106, USA"},{"name":"6 Parke-Davis Laboratory for Molecular Genetics, Alameda, CA 94502, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2000,6,1]]},"reference":[{"key":"2023051200045216600_DEVELOP_127_11_2347C1","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1242\/dev.120.3.613","article-title":"Induction of a second neural axis by the mouse node","volume":"120","author":"Beddington","year":"1994","journal-title":"Development"},{"key":"2023051200045216600_DEVELOP_127_11_2347C2","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1002\/(SICI)1097-0177(199604)205:4&lt;471::AID-AJA10&gt;3.0.CO;2-4","article-title":"Cell proliferation in mammalian gastrulation: the ventral node and notochord are relatively quiescent","volume":"205","author":"Bellomo","year":"1996","journal-title":"Dev. 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