Overo lethal white syndrome (OLWS) is an inherited syndrome of foals born to American Paint Horse parents of the overo coat-pattern lineage. Affected foals are totally or almost totally white and die within days from complications due to intestinal aganglionosis. Related conditions occur in humans and rodents in which mutations in the endothelin receptor B (EDNRB) gene are responsible. EDNRB is known to be involved in the developmental regulation of neural crest cells that become enteric ganglia and melanocytes. In this report we identify a polymorphism in the equine EDNRB gene closely associated with OLWS. This Ile to Lys substitution at codon 118 is located within the first transmembrane domain of this seven-transmembrane domain G-protein-coupled receptor protein. All 22 OLWS-affected foals examined were homozygous for the Lys118 EDNRB allele, while all available parents of affected foals were heterozygous. All but one of the parents also had an overo white body-spot phenotype. Solid-colored control horses of other breeds were homozygous for the Ile118 EDNRB allele. Molecular definition of the basis for OLWS in Paint Horses provides a genetic test for the presence of the Lys118 EDNRB allele and adds to our understanding of the basis for coat color patterns in the horse.
"There are a number of mutants in livestock and pets that have been maintained by heterozygote advantage adding significantly to the number of polymorphisms maintained by heterozygote advantage in populations. Here I have given details of the 12 best documented examples, seven of them in livestock and five in pets (see other potential examples in Santschi et al. 1998; Pailhoux et al. 2001; Cavanagh et al. 2007; Qin et al. 2010; Reissman and Ludwig 2013; Kadri et al. 2014). These mutants with a heterozygote advantage constitute a great diversity of mutation types (Tables 1 and 2) with some causing phenotypic and fitness effects because of small changes, either nonsynonymous substitutions in coding regions or small insertions or deletions that cause reading-frame changes. "
"For both receptors, the activating ligands have not been identified yet in zebrafish. In mammals, where Endothelin signalling promotes the development of melanocytes, mutations in Ednrb or its ligand Endothelin 3 (Edn3) lead to a reduction of melanocytes, as well as aganglionosis caused by a strong reduction in sensory gut neurons (Baynash et al., 1994; Gariepy et al., 1996; Hosoda et al., 1994; Kunieda et al., 1996; Metallinos et al., 1998; Santschi et al., 1998). Similar reductions in the number of melanocytes were observed in mice carrying a knock-out allele of the endothelin-converting enzyme 1 (Ece1). "
[Show abstract][Hide abstract] ABSTRACT: Colour patterns of adult fish are composed of several different types of pigment cells distributing in the skin during juvenile development. The zebrafish, Danio rerio, displays a striking pattern of dark stripes of melanophores interspersed with light stripes of xanthophores. A third cell type, silvery iridophores, contributes to both stripes and plays a crucial role in adult pigment pattern formation. Several mutants deficient in iridophore development display similar adult phenotypes with reduced numbers of melanophores and defects in stripe formation. This indicates a supporting role of iridophores for melanophore development and maintenance. One of these mutants, rose (rse), encodes the Endothelin receptor b1a. Here we describe a new mutant in zebrafish, karneol (kar), which has a phenotype similar to weak alleles of rse with a reduction in iridophore numbers and defects of adult pigment patterning. We show that, unlike rse, kar is not required in iridophores. The gene defective in the kar mutant codes for an endothelin-converting enzyme, Ece2, which activates endothelin ligands by proteolytic cleavage. By morpholino-mediated knockdown, we identify Endothelin 3b (Edn3b) as the ligand for endothelin receptor signalling in larval iridophores. Thus, Endothelin signalling is involved in iridophore development, proliferation and stripe morphogenesis in larvae as well as adult zebrafish. In mammals the pathway is required for melanocyte development; therefore, our results indicate a previously unrecognized close evolutionary relationship between iridophores in zebrafish and melanocytes in mammals.
Biology Open 05/2014; 3(6). DOI:10.1242/bio.20148441 · 2.42 Impact Factor
"The naturally occurring horse variant of Hirschsprung's disease is known as ileocolonic aganglionosis (ICA) or overo lethal white syndrome (OLWS) [Brashier and Geor, 1995; Metallinos et al., 1998; Lightbody, 2002; Finno et al., 2009], which is a fatal condition, and foals die within the first few days after birth due to an obstruction-induced intestinal severe colic and paralytic ileum [McCabe et al., 1990; Parry, 2005]. In both horses and humans, aganglionosis results from a congenital disorder of neural crest cell migration throughout the intestine (craniocaudal migration theory) [Okamoto and Ueda, 1967; Santschi et al., 1998; Lightbody, 2002]. "
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