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Prepublished online as a Blood First Edition Paper on July 24, 2003; DOI 10.1182/blood-2003-05-1468. This Article Full Text (PDF) All Versions of this Article: 2003-05-1468v1 102/10/3548    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Chandra, S. Articles by Williams, D. A Search for Related Content PubMed PubMed Citation Articles by Chandra, S. Articles by Williams, D. A Social Bookmarking                   What's this? Submitted May 9, 2003 Accepted June 28, 2003 A rare complex DNA rearrangement in the murine Steel gene results in exon duplication and a lethal phenotype Saurabh Chandra, Reuben Kapur, Nadia Chuzhanova, Victoria Summey, David Prentice, Jane Barker, David N Cooper, and David A Williams* Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Life Sciences and School of Graduate Studies, Indiana State University, Terre Haute, IN, USA Herman B Wells Center for Pediatric Research, Indiana School of Medicine, Indianapolis, IN, USA Institute of Medical Genetics, University of Wales College of Medicine, Cardiff, United Kingdom The Jackson Laboratories, Bar Harbor, ME, USA * Corresponding author; email: david.williams{at}cchmc.org. Kit ligand (Kitl), encoded by the Steel (Sl) locus, plays an essential role in hematopoiesis, gametogenesis, and melanogenesis during both embryonic and adult life. We have characterized a new spontaneous mutant of the Sl locus in mice designated KitlSl-20J, that arose in the breeding colony at Jackson Laboratories. Heterozygous KitlSl-20J mice display a white belly spot and intercrossing results in an embryonic lethal phenotype in the homozygous state. Analysis of homozygous embryos demonstrated a significant reduction in fetal liver cellularity, colony forming unit-erythroid (CFU-E) progenitors and a total absence of germ cells. Although expressed in vivo, recombinant mutant protein demonstrated loss of bioactivity that was correlated with lack of receptor binding. Analysis of the Sl gene transcripts in heterozygous KitlSl-20J mice revealed an in-frame tandem duplication of exon 3. A long-range PCR strategy using overlapping primers in exon 3 amplified a ~ 7 kb product from DNA isolated from heterozygous KitlSl-20J mice but not from wild-type DNA that contained sequences from both introns 2 and 3 and an inverted intron 2 sequence, suggesting a complex rearrangement as the mechanism of the mutation. "Complexity analysis" of the sequence of the amplified product strongly suggests that local DNA motifs may have contributed to the generation of this spontaneous KitlSl-20J allele, likely mediated by a two-step process. The KitlSl-20J mutation is a unique KitlSl allele and represents an unusual mechanism of mutation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. A. Bedell and A. M. Zama Genetic Analysis of Kit Ligand Functions During Mouse Spermatogenesis J Androl, March 1, 2004; 25(2): 188 - 199. [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020