Mutations knockdown resistance

Naturally Occurring Point Mutations in the Sodium Channel Gene Responsible for Knockdown Resistance to Pyrethroids. 

The target biomolecules for DDT and the pyrethroids are the sodium channels in the axon. One very common type of resistance is the so-called knockdown resistance, or kdr resistance. In this case one or more amino acids have been changed due to point mutation so that DDT or pyrethroids do not bind. Whereas houseflies that are resistant due to the presence of the DDT dehydrochlorinase type of glutathione transferase will be paralyzed by DDT, it is found that when DDT has been detoxicated, the flies wake up and... 

Abundant use of one of the most commonly used insecticides in crop protection, pyrethroids, has led to the development of resistance in many insect species.One of the most important mechanisms is that of knockdown resistance (kdr), caused by several mutations in the gene (L1014F and M918T), which confers crossresistance to the entire class of pyrethroids. Another problem is that most insecticides cause toxicity in organisms other than insects because of the general conservation of the voltage-gated Na" " channel structure... 

Genetic analysis and biochemical studies have shown that kdr resistance is linked to one of the building blocks of the sodium channels in the axon (the gene for the so-called a-subunit). The gene has been sequenced in R-and S-flies. The substitution of a leucine residue with a phenylalanine residue makes the difference. Equivalent mutations have been found in pyre-throid-resistant strains of several other insect species. Two point mutations in the a-subunit of the sodium channels are associated with super-kdr resistance. Such mutations have been detected in the housefly, horn fly, diamond moth, and body louse. It may cause several hundred-fold resistance. It is interesting to note that if knockdown, and not death, is used as the endpoint, the resistance level is much higher. 

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