A team of Japanese and US researchers has managed to create transgenic zebrafish, using genetically-modified sperm grown in the laboratory. Researchers at the Fukui Prefectural University in Obama, Japan and the US National Human Genome Research Institute (NHGRI), say their findings have implications for a wide range of research areas, from developmental biology to gene therapy. 'To our knowledge, this is the first time that sperm cells have been cultured entirely in vitro and used to produce a transgenic animal' said study author Shawn Burgess. The findings are published in the online edition of the journal Proceedings of the National Academy of Science.
The scientists have developed a technique for taking immature sperm cells (spermatagonia) from a male zebrafish, and keeping them alive in the laboratory long enough to infect them with foreign genes, using a type of virus. 'The secret to our success was the idea of placing a layer of special 'feeder cells' under the spermatagonia in the laboratory dish' said team leader Noriyoshi Sakai. The researchers then managed to grow the genetically-altered spermatagonia into mature sperm, which they used to fertilise zebrafish eggs in the laboratory.
The procedure has a low success rate - only six of 1410 eggs exposed to the genetically altered sperm were successfully fertilised. However, the transgenic fish created in this way would have the foreign gene present in every cell of their body, including their egg and sperm cells. Current transgenic techniques often produce 'mosaic' animals, whose bodies are mixture of normal and genetically altered cells. The advantage of the new technique is that it would produce animals that would always pass on their genetic alteration to the next generation.
Scientists use transgenic animals to study the effects of genetic mutations involved in disease, or to find out what a particular gene does in the body. Commenting on the new study, Eric Green, director of NHGRI said: 'This is an outstanding example of our efforts to build upon the foundation laid by the Human Genome Project. Burgess speculates that if the procedure could be adapted to human sperm, it could one day be used to correct human genetic diseases before fertilisation. However, such germline gene therapy is currently outlawed in the UK, and many other countries. 'There's a huge path to cross before that happens. No-one has ever made such an application' said a spokesman for the UK's Human Fertilisation and Embryology Authority.