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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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