Reproductive restraint revealed in mice

Killing rodents, whether by traps, chemicals or diseases, will never be an efficient long-term management option. Such attempts at pest control will always be fighting against the natural strengths of the pest; their mobility and their extraordinary reproductive capacity. For example, one pair of house mice is theoretically capable of producing over six hundred offspring in just six months, with females producing a litter every three weeks. However many we manage to kill, their remaining cousins will always be able to replace lost numbers. This at least is one of the main arguments behind a research programme that is developing an immuno-contraceptive for pest species: an agent that could disturb the reproductive functions of wild pest populations, thereby limiting their size and damage. Immuno-contraception would, it is argued, be a more effective, and a more ethical approach to rodent control than the current 'lethal' methods.

credit: CSIRO Rodent Research Group

The research team, which is based at the Pest Animal Control Co-operative Research Centre, in Canberra, has already demonstrated that such a contraceptive is a possibility. It works by inserting the DNA for a protein which is vital for mouse-egg fertilisation, into a mouse virus. The protein in question forms part of the coating of a developing egg, and is what enables sperm to bind to the egg, and consequently fertilise it. When mice are infected with the engineered (or recombinant) virus, both the reproductive protein and viral proteins are expressed in infected cells, and the mouse's immune system produces antibodies against these proteins. These antibodies spread to the reproductive tract of the mouse, where some disrupt the normal development of follicles and eggs, resulting in infertility.

The researchers first attempts to develop the technique used an Ectromelia virus which causes the disease known as mousepox. However, this virus is not naturally present in Australia, where the team are keen to advance the technology for use in controlling plagues of house mice (Mus domesticus). So the focus was then centred on an alternative virus, murine cytomegalovirus (MCMV), which is highly prevalent in Australian mice and specific to the house mouse. Laboratory tests with the recombinant MCMV expressing mouse egg coat protein have proved successful. In some laboratory strains of mice, no litters were produced for 200 days after infection whilst an uninfected control group produced approximately three hundred pups in the same period. In other laboratory strains the response was less severe, and reasons for this are currently being explored. Recent experiments have shown that wild mice held in the laboratory and infected with the recombinant virus also experience infertility for extended periods (no litters for more than 200 days).

credit: CSIRO Rodent Research Group

The future applicability of the work will depend on a number of issues being resolved. Extensive research will be needed to build a clear picture of how the natural virus is transmitted in the wild, and how genetically modifying it to include the protein DNA may affect transmission. An important question is whether the modified virus will create an immune response leading to high levels of infertility in a population that has already experienced the natural infection. The researchers will also need to establish what proportion of the mouse population would need to be infected by the virus in order to bring the total number down to a 'tolerable' level. For instance, in one test, 67% of females were surgically sterilised and, at the end of an 18 week period, the total population had grown to 104 animals, in comparison with 221 animals in a control group. A third key area of concern relates to whether the sterilising effect of the virus will disrupt hormone production, and hence the normal social and reproductive relations between mice. This could be important both from an ethical viewpoint, and in terms of the effectiveness of the method as a population control. For example, in some rodent species, a dominant female will suppress reproductive behaviour in subordinate females. If, following infection with the recombinant virus, this behaviour were to stop, a larger number of females might be able to breed, leading to an increased rather than a reduced population.

The future of immuno-contraceptive technology will clearly depend, not only on scientific feasibility, but also on social and ethical considerations. Any plan to release an artificially created virus into the wild is likely to provoke strong opposition, not least because once the virus was released, its spread would be out of human control. A more acceptable option could be an infertility agent that could not spread automatically in the rodent population, but would instead need to be delivered in the form of bait. The team has considered such a method, and its advantages in terms of public acceptance were recognised. However, a bait-based system would be more expensive, require greater human labour, and present the usual problems experienced by baiting, such as timing application to match breeding cycles, and bait aversion. It may also prove impossible to infect a sufficient proportion of the rodent population to achieve the control effect, particularly in remote areas with difficult terrain.

There are many areas that still need to be resolved with regard to successful fertility control methods but it has been demonstrated that it can be achieved and the risks and problems of developing such an ecologically-based pest management approach must be viewed in the context of current control methods, including the extensive use of poisons which are fatal and non-specific.

Back to Menu