Dr Jess Buxton
Progress Educational Trust
26 April 2004
 [BioNews, London]
Does the birth of the world's first 'parthenogenetic' mouse, created using eggs from two female mice, really mean that men will soon be redundant? Well, no - if anything, it confirms that for mammals, sexual reproduction is the only way to make babies, thanks to a phenomenon known as imprinting. Last week's publication of the technique used to create 'Kaguya', by a team of Japanese scientists, inevitably attracted a fair amount of coverage, cartoons and comment in the popular press. The achievement also caused a stir in the scientific community, but for different reasons - most of which did not hit the headlines.
Scientists have known for some time that so-called 'parthenogenetic reproduction' - in which an egg cell begins to grow and develop without being fertilised by a sperm - is the preserve of some reptiles, amphibians, fish and insects. For mammals to reproduce, an egg must fertilise a sperm, so that the developing embryo has one set of genes from the mother, and one from the father. For reasons that are still unclear, the genetic material of mammal eggs and sperm is 'labelled', as either maternal or paternal in origin. This process, unique to mammals, is known as imprinting. It takes the form of a set of molecular 'stamps', which cause a particular gene to be switched on or off in the growing embryo. For some genes, the paternal copy is shut down, whereas for some others, the mother's contribution is silenced. So to develop properly, a mammal embryo must have two, complementary genomes, one from each parent.
The Japanese researchers found that they could override this natural barrier to asexual reproduction in mice. They first bred genetically altered 'knock-out mice', which were missing a key imprinted gene. This in turn affected the imprinting stamp on another gene, so that the eggs produced by the mice resembled sperm - in terms of their genes, at least. Much to the surprise of the team, and other scientists, tinkering with just two imprinted genes had some sort of 'ripple effect' on other genes: when fused with normal mouse eggs, the resulting embryos could develop into full-term mouse pups. The procedure was complex, intricate and not very reliable, with just eight mouse pups being born following 457 egg 'reconstructions'. But the fact that it worked at all was unexpected, and shows for the first time that imprinting is the sole guardian of sexual reproduction.
As well as providing basic insights into the imprinting process, the new findings have implications for research into optimising IVF procedures, and somatic cell nuclear transfer (SCNT) experiments. There is some evidence that embryo culturing conditions can affect imprinting, leading to a slightly increased risk of some rare genetic disorders, such as Beckwith-Wiedemann syndrome, in children born following IVF. And problems with imprinting are probably behind the low success rates experienced by researchers trying to clone animals. Last week's paper by Tomohiro and colleagues may not mark the end of human reproduction as we know it, as some commentators have suggested, but it could pave the way for a greater understanding of mammalian reproduction, both in and out of the laboratory.
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Reproduced from BioNews with permission, a web- and email-based source of news, information and comment on assisted reproduction and human genetics, published by Progress Educational Trust.
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