Press Release 8/12/2000
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The 'terminator technology that genetic engineers seed sterility to
enforce corporate patents on seed has been universally condemned and
rejected as being contrary to human rights. They are now being promoted as
a means of preventing gene flow by the US and UK Govts, and ISIS has
uncovered that terminator crops are undergoing field trials in the UK, and
have been grown elsewhere in Europe since 1990 (See ISIS Press Release 6
Dec. 2000).
ISIS has warned also of the dangers involved in the technology, and
predicted that the recombinase enzyme used will scrambled genomes (see "Terminator
in new guises" ISIS News #3, December 1999.This has now been
demonstrated in transgenic mice engineered with the recombinase.
The recombinase Cre is part of the 'site-specific recombination' Cre/lox
system originally isolated from the bacteriophage (bacterial virus) P1.
Cre catalyses recombination between two lox sites, splicing out any
stretch of DNA in between. The lox site is a 34 basepair element
consisting of 13 basepair inverted repeat separated by a core of 8
basepairs. In order to work, the 8 basepair core of the two lox sites have
to be in the same orientation.
The system is not only used in plants, but extensively exploited in
transgenic mice. Studies in the test-tube have shown that Cre recombinase
can catalyze recombination between DNA sequences found naturally in yeast
and mammalian genomes. These 'illegitimate sites' often bear little
sequence similarity to the lox element. However, there have been no
reports on such illegitimate recognition in the animals or plants
themselves. And there have even been pilot studies using the Cre/lox
system in human gene therapy.
In a study just published (1), researchers in the United States showed
that high levels of Cre expression in the spermatids of heterozygous
transgenic mice leads to 100% sterility in the males, despite the absence
of any lox sites. Heterozygous mice carry only one copy of the Cre
recombinase gene.
The sterility is caused directly by the recombinase enzyme scrambling
the genome, essentially by breaking and rejoining DNA at inappropriate
sites on the same or different chromosomes. The researchers have
pinpointed the genome scrambling event to the time at which the two
'daughter' spermatids and their paired chromosomes have just separated
from each other; but are still joined by a 'cytoplasmic bridge'. This is
enough to allow the enzyme to pass from the spermatid containing the
recombinase gene to the other which does not, thereby to scramble up the
chromosomes of both the transgenic and nontransgenic spermatid. The result
is 100% sterility. Embryos fertilized by these sperms arrest predominantly
at the 2 cell stage, and do not go beyond the four cell stage.
The researchers warn: "These results indicate that Cre can catalyze
illegitimate recombination having overt pathological consequences in
animals." A similar recombination system is found in animals
containing the RAG recombinases. There, illegitimate recombinations in
somatic cells are linked to human leukemias.
1. Schmidt, E.E., Taylor, D.S., Prigge, J.R., Barnett, S. and Capecchi,
M.R. (2000). Illegitimate Cre-dependent chromosome rearrangements in
transgenic mouse spermatids. PNAS 97, 13702-13707.
Drs. Mae-Wan Ho and
Joe Cummins
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