Identification and characterisation of dominant ivermectin resistant genes in Caenorhabditis elegans

Abstract

Ivennectin (IVM) is a potent anthelmintic which is lethal to Caenorhabditis elegans when included in nutrient agar growth medium at concentrations above 2 ng/mL. Recessive mutations imparting resistance to 5 nglmL are obtainable in "lout of 204 mutagenised genomes" (0.05 Methyl methanesulfonate) and arise spontaneously at 1.7xlO-5 (Kim and Johnson, 1991). These "low-level" resistance mutations (resistant to 5-30 nglmL IVM) occur at about thirty loci (Kim and Johnson, 1991). Dominant IVM resistant alleles have been observed under field conditions in Haemonchus contortus and these are resistant to low levels of IVM in in vitro larval development assays (Lacey, Redwin et. ai., 1990; Martin and Turney, 1992; LeJambre, 1993; LeJambre, Gill et ai., in press). C. eiegans was used as a model to study IVM resistance in parasitic nematodes. To identify loci at which dominant IVM resistance alleles occur, a C. eiegans mutagenesis screen was undertaken to obtain dominant IVM resistance (5 ng/mL) alleles. The rate of mutagenesis for dominant IVM resistance was found to be 7.9 xl 0-7, indicating that these alleles are much rarer than recessive alleles.