title: Zebrafish mutants calamity and catastrophe define critical pathways of gene-nutrient interactions in developmental copper metabolism.
abstract: Nutrient availability is an important environmental variable during development that has significant effects on the metabolism, health, and viability of an organism. To understand these interactions for the nutrient copper, we used a chemical genetic screen for zebrafish mutants sensitive to developmental copper deficiency. In this screen, we isolated two mutants that define subtleties of copper metabolism. The first contains a viable hypomorphic allele of atp7a and results in a loss of pigmentation when exposed to mild nutritional copper deficiency. This mutant displays incompletely penetrant skeletal defects affected by developmental copper availability. The second carries an inactivating mutation in the vacuolar ATPase that causes punctate melanocytes and embryonic lethality. This mutant, catastrophe, is sensitive to copper deprivation revealing overlap between ion metabolic pathways. Together, the two mutants illustrate the utility of chemical genetic screens in zebrafish to elucidate the interaction of nutrient availability and genetic polymorphisms in cellular metabolism.
authors.affiliation: Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St Louis, MO, USA.
authors.forename: Erik C
authors.initials: EC
authors.lastname: Madsen
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Gitlin
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000483:Alleles; D000818:Animals; D002478:Cells, Cultured; D003300:Copper / Q000378:metabolism*; D000073840:Copper-Transporting ATPases; D004625:Embryo, Nonmammalian / Q000378:metabolism; D006801:Humans; D020460:Melanosomes / Q000378:metabolism; D007706:Menkes Kinky Hair Syndrome / Q000196:embryology / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D010641:Phenotype; D021381:Protein Transport; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics* / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C515592:Atp7a protein, zebrafish; D029961:Zebrafish Proteins; D003300:Copper; D000251:Adenosine Triphosphatases; D000073840:Copper-Transporting ATPases