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[SANET-MG] the scorpion and the genetic engineer



August 2, 2005
Prof. Joe Cummins
“The scorpion and the oil rapeseed genetic engineer”
Genes from scorpion toxins have begun to be employed in the genetic engineering of crop plants as a means of controlling insect pests. Aesop’s fable “The Scorpion and the Frog” provides a useful reminder about the scorpion. A scorpion and a frog meet on the bank of a stream and the scorpion asks the frog to carry him across on its back. The frog asks, "How do I know you won't sting me?" The scorpion says, "Because if I do, I will die too." The frog is satisfied, and they set out, but in midstream, the scorpion stings the frog. The frog feels the onset of paralysis and starts to sink, knowing they both will drown, but has just enough time to gasp "Why?" Replies the scorpion: "Its my nature..." The problem with using the scorpion toxin is that it may start out the planting specifically toxic to insects and end the planting somewhat or fully toxic to mammals. Chinese researchers modified Brassica napus (oilseed rape) with two insect resistance genes, A gene for scorpion toxin (BmkIT) and a gene for chitinase (chi). The genetic modification included the double 35S promoter driving the BmkIT gene followed by the Nos terminator this was accompanied by the chitinase gene driven by a 35S CamV promoter and terminated by a transcription terminator form CaMV. Along with a Kanamycin resistance marker (NPTII) regulated by nopaline synthetase promoter and terminator. The transformed plants ahd high level production of the scorpion toxin and chitinase enzyme The report noted that the scorpion toxin was insect specific but did not go into detail about the origin and specificity of the toxin(1). Bmk IT was found to depress sodium channels in the cells of insects and mammals. It was suggested that the toxin could bind to peripheral nerve cells but not the nerve cells of the mammalian central nervous system (2). Bmk was active in behavior and on the oncoprotein c-Fos inducuced by the carcinogen formalin of rats. The accumulation of particular proteins, because they are over-expressed or because they are not normally degraded, is sufficient for cell transformation. Although these proteins are constituents of normal cells, they receive the name of proto-oncoproteins because of their transforming capacity when unregulated. One of these proto-oncoproteins is c-Fos. It has been postulated that c-Fos forms a complex with another proto-oncoprotein, c-Jun, and is imported into the nucleus where it binds to DNA and regulates the expression of target genes important for cell growth. Both behavior and c-Fos induction was suppressed by adminsistation of BmkIT(3) The toxin Bmk MI (related to BmkIT ) is active in both insects and mammals, site specific mutation of 14 C-terminal amin acids of the toxin resulted in large mutant dependent differences. The alterations varied from total insect specificity to much higher mammalian specificity (4). One implication of such studies is that the toxin gene could be used in a food crop such as oilseed rape but that the specificity of the the toxin could readily be altered in somatic or reproductive tissue to cause the toxin to be active to some degree (either small or large) by mutations in the inserted gene. Such mutations would be both spontaneous and induced by environmental factors such as ozone pollution or chemical pesticides. Turning to the inserted insect chitinase gene , insect chitinase has been used to create insect tolerance in transgenic crops. Little discussion has been provided in the published studies concerning the potential allergenicity of insect chitinases. Chitinases have been found to be potent allergens, for example , the most potent allergen in dust mite insects is insect chitinase (5). Insect chitinases should be presumed to be allergens until proven to be free of allergenicity. A good deal more research is needed to insure that the combined scorpion toxin and insect chitinase crops are not highly toxic to those who consume the crops as food or feed. Like the scorpion of Aesop’s fable the scorpion toxin seems bound to sting those who consume the crop and those who invented the crop alike.
Reference
1. Wang J, Chen Z, Du J, Sun Y. and Liang A. Novel insect resistance in Brassica napus developed by transformation of chitinase and scorpion toxin genes. Plant Cell Rep. 2005 Jul 19; [Epub ahead of print] 2. Li YJ, Tan ZY and Ji YH. The binding of BmK IT2, a depressant insect-selective scorpion toxin on mammal and insect sodium channels. Neurosci Res. 2000 Nov;38(3):257-6 3. Zhang XY, Bai ZT, Chai ZF, Zhang JW, Liu Y and Ji YH. Suppressive effects of BmK IT2 on nociceptive behavior and c-Fos expression in spinal cord induced by formalin. J Neurosci Res. 2003 Oct 1;74(1):167-73 4. Liu LH, Bosmans F, Maertens C, Zhu RH, Wang DC and Tytgat J. Molecular basis of the mammalian potency of the scorpion alpha-like toxin, BmK M1. FASEB J. 2005 Apr;19(6):594-6 5. McCall C, Hunter S, Stedman K, Weber E, Hillier A, Bozic C, Rivoire B and Olivry T. Characterization and cloning of a major high molecular weight house dust mite allergen (Der f 15) for dogs. Vet Immunol Immunopathol. 2001 Feb 10;78(3-4):231-47
	
	

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