Interstitial deletion of the endothelin-b receptor gene in the spotting lethal (sl) rat

Isabella Ceccherini, An Ling Zhang, Ivana Matera, Gouchen Yang, Marcella Devoto, Giovanni Romeo, Daniel T. Cass

Research output: Contribution to journalArticlepeer-review


The autosomal recessive spotting lethal (sI) rat phenotype is characterized by absence of intramural ganglion cells in the entire colon and distal small bowel, thus resembling the human Hirschsprung (HSCR) disease. A strategy for identifying the gene responsible for this rat defect was initiated by backcrossing DA × sl rats. After excluding linkage with two candidate genes, RET and Endothelin-3 (EDN3), a highly significant lod score (Z = 47.05 at θ = 0) was found between the Endothelin-B Receptor (EDNRB) gene and the sI phenotype. The exon-intron structure of this rat gene was reconstructed and each exon of the sl rat was screened for possible mutations. A 301 bp interstitial deletion, encompassing the distal half of the first coding exon (exon 2) and the proximal part of the adjacent intron, was demonstrated. This deletion results in two transcriptional products, 270 and 238 bp shorter than wild type cDNA. The discovery of the molecular defect underlying the sI rat phenotype should contribute to the understanding of the genetic heterogeneity of HSCR in man.

Original languageEnglish
Pages (from-to)2089-2096
Number of pages8
JournalHuman Molecular Genetics
Issue number11
Publication statusPublished - Nov 1995

ASJC Scopus subject areas

  • Statistics, Probability and Uncertainty
  • Applied Mathematics
  • Public Health, Environmental and Occupational Health
  • Molecular Biology
  • Genetics(clinical)
  • Genetics


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