{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T04:22:50Z","timestamp":1770524570489,"version":"3.49.0"},"reference-count":39,"publisher":"The Company of Biologists","issue":"3","license":[{"start":{"date-parts":[[1993,3,1]],"date-time":"1993-03-01T00:00:00Z","timestamp":730944000000},"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":[[1993,3,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>The lethal spotted (ls) mouse has been used as a model for the human disorder Hirschsprung\u2019s disease, because as in the latter condition, ls\/ls homozygotes are born without ganglion cells in their terminal colons and, without surgical intervention, die early as a consequence of intestinal obstruction. Previous studies have led to the conclusion that hereditary aganglionosis in ls\/ls mice occurs because neural crest-derived enteric neuroblasts fail to colonize the distal large intestine during embryogenesis, perhaps due to a primary defect in non-neuroblastic mesenchyme rather than migrating neuroblasts themselves. In this investigation, the latter issue was addressed directly, in vivo, by comparing the distributions of ls\/ls and wild-type neurons in aggregation chimeras. Expression of a transgene, D H-nlacZ, in enteric neurons derived from the vagal neural crest, was used as a marker for ls\/ls enteric neurons in chimeric mice. In these animals, when greater than 20% of the cells were wild-type, the ls\/ls phenotype was rescued; such mice were neither spotted nor aganglionic. In addition, these \u2018rescued\u2019 mice had mixtures of ls\/ls and wildtype neurons throughout their gastrointestinal systems including distal rectum. In contrast, mice with smaller relative numbers of wild-type cells exhibited the classic ls\/ls phenotype. The aganglionic terminal bowel of the latter mice contained neither ls\/ls nor wild-type neurons. These results confirm that the primary defect in ls\/ls embryos is not autonomous to enteric neuroblasts, but instead exists in the non-neuroblastic mesenchyme of the large intestine.<\/jats:p>","DOI":"10.1242\/dev.117.3.993","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T01:19:39Z","timestamp":1619399979000},"page":"993-999","source":"Crossref","is-referenced-by-count":47,"title":["Aggregation chimeras demonstrate that the primary defect responsible for aganglionic megacolon in <i>lethal spotted<\/i> mice is not neuroblast autonomous"],"prefix":"10.1242","volume":"117","author":[{"given":"Raj P.","family":"Kapur","sequence":"first","affiliation":[{"name":"Department of Laboratories 1 , CH-37, Children\u2019s Hospital and Medical Center, PO Box 5371, Seattle, Washington 98105, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia","family":"Yost","sequence":"additional","affiliation":[{"name":"Department of Biochemistry 2 , Howard Hughes Medical Institute, University of Washington, SL-15, Seattle, Washington 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard D.","family":"Palmiter","sequence":"additional","affiliation":[{"name":"Department of Biochemistry 2 , Howard Hughes Medical Institute, University of Washington, SL-15, Seattle, Washington 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[1993,3,1]]},"reference":[{"key":"2024121722463550500_DEVELOP_117_3_993C1","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/0012-1606(89)90217-0","article-title":"Transient catecholaminergic (TC) cells in the vagus nerves and bowel of fetal mice: relationship to the development of enteric neurons","volume":"132","author":"Baetge","year":"1988","journal-title":"Dev. 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