Brussels, 24 Mar 2003
European scientists have recently developed a new method for studying gene mutations, which could lead to better understanding and treatment of childhood leukemias in humans.
While removing and adding small segments of DNA to an organism's genome has been widely employed to improve understanding of human diseases, scientists have had difficulties in developing methods to examine large molecules such as genes. In particular, scientists from the European molecular biology laboratory (EMBL) and the Technical University in Dresden were very interested in the mixed lineage gene leukemia (MII) which is known to become defective and lead to leukemia.
'There are many things that can go wrong in this gene and we wanted to construct a version of it that would allow us to test as many aspects of the problem as possible,' said Giussepe Testa from the Technical University in Dresden.
Organisms like mice have proteins in their body that circulate through their cells repairing any loose fragments of DNA that have familiar sequences. Scientists were aware that this process, known as homologous recombination, was also present in bacteria and went in search of a strain to study.
The group quickly identified the bacterial factors involved and turned them into a new tool called Red/ET recombination which increases the size of DNA that can be engineered by more than ten times.
Using this tool, the scientific team led by Dr Testa were able to construct a large complex 'cassette' of the MII gene and insert it into a mouse in the place of its normal gene.
The artificial gene contains two defects in the genetic sequence that have been linked with leukemia. Using control switches, each defect can be switched on and off.
'We can study each mutation independently, or watch how they act together, or control the time at which each one acts. This will give us a new look at subtle relationships between multiple defects,' noted Dr Testa.
It is expected that such developments will enable scientists to better understand disease susceptibilities. 'This aspect of making mouse models will become increasingly more important for authentic modelling of human disease susceptibility and the way organisms respond to drugs, and we think that our work shows the way to set up these models,' concluded Mr Testa.