Model organisms: The mouse

28/8/02. By Richard Twyman

The mouse is closely related to humans so most human genes have functional mouse counterparts and the genome is organised in a very similar manner.

The mouse is the model organism most closely related to humans. The mouse and human genomes are approximately the same size, contain the same number of genes and show extensive synteny (conserved gene order). Most human genes have mouse counterparts and the functions of these genes are closely related. Mutations that cause diseases in humans often cause similar diseases in mice. Importantly, mice have genes that are not represented in other animal models (the fruit fly and nematode worm), including the genes of the immune system.

The similarities discussed above probably apply to most mammals, but the mouse has further properties that make it an ideal model organism. Mice are small, easy to maintain in the laboratory and (compared to most mammals) have a short breeding cycle (about 2 months). They can produce 10-15 offspring per litter and approximately one litter every month. This makes them suitable for genetic analysis. Many mutants are available and new mutations can be introduced easily by irradiation, feeding with chemical mutagens or inserting DNA fragments into the genome to interrupt genes.

The mouse is the model organism most closely related to humans.

The suitability of mice for genetic analysis is enhanced by the availability of different species, such as Mus musculis and Mus spretus, which can be used for interspecific crosses. The advantage of this approach is that the different species are likely to have different DNA sequences at most polymorphic sites in the genome. Therefore, the interspecific hybrids produced from such crosses are extensively heterozygous and can be used to make finely detailed genetic maps (see Linkage analysis). Large-scale crosses can therefore be carried out to accurately map disease genes. It is often quicker to map a mouse disease gene and use its location to find the position of the equivalent human gene than it is to map the human gene directly. Advanced breeding strategies can be used to make specialised strains such as congenics, which are genetically identical with the exception of polymorphism for one specific gene.

As if the above were not enough, the mouse also has a string of unique technological advantages. Gene transfer technology is highly advanced, so transgenic mice can be created carrying any foreign gene of interest. Also, the mouse is the only vertebrate species in which pre-selected genes can be deliberately mutated in a precise manner (see Knockout mice). This means it is possible to create exact replicas of the genetic defects that cause diseases in humans. For some reason, certain complex diseases are difficult to replicate in the mouse and in such cases the rat is often a suitable alternative.