The common mouse (Mus musculus L.) is a pest for householders, a pet for animal lovers, a blessing for molecular biologists, and a hero for some psychologists. It even shared an Oscar: Cliff Robertson won his 1968 Best-Actor award for beating Algernon, a cute albino mouse, in racing in a "maze (Nelson et al. 1968). It is not clear, though, whether Algernon made it to the ceremony. Mice have accompanied human populations since prehistoric times. Similar to rats, they originated in Asia, and from there spread to the rest of the world. They were occasionally used for amusement in both East and West, and a mutant, the 'waltzing' mouse (see below), had been bred in China and Japan specifically for this purpose. Throughout the Middle Ages, mice were used in magic and folk medicine (Thorndike 1923). The first documented use in scientific investigation was by Robert Hook, who in 1663/64 experimented on the survival of the mouse in compressed air, hoping to gain some insight about the ability of man to breathe under water (Nichols 1994). But mice only found their way into the routines of laboratory life during the nineteenth century, when they were started to be employed in large numbers in the study of genetics. Many laboratory strains used today can be traced almost a century back to a few commercial colonies in the USA (Green et al. 1966; Hogan et al. 1994). DNA analysis shows that several of these strains originated from a single female of the subspecies Mus musculus domesticus, the common house mouse. But as genetic material from other subspecies has been introduced over time into the genetic pool of the laboratory mouse, standard inbred strains are referred to as M. musculus only. The genetic making of the mouse can now be easily manipulated (see below), and new strains are produced on demand (mice were also already cloned from somatic cells; Wakayama et al. 1998).
The mouse has a lot to offer to biologists and psychologists alike. It is a small mammal (20-35 g), but not small enough to make the life of anatomists and physiologists miserable. The size of the brain is manageable. The generation time is 3-4 months, and the litter size six to eight in inbred lines. Handling is easy and the food inexpensive. Only the smell of the mouse colony is a potential obstacle. The mouse is an agile, social animal (Williams and Scott 1953). It has a rich behavioural repertoire, and is quick to learn, especially in natural situations that involve the chemical senses, spatial information, and social interactions. Perhaps the "classic example of mouse behavioural analysis is that of the dancing (waltzing) mouse by Yerkes (1907). Even Pavlov, whose favourite experimental "subject was the dog ("classical conditioning), switched to the mouse to study the inheritance of conditioned reflexes (Razran 1958). Since those early days, mice have been used extensively in the study of learning and memory (for a useful selection of paradigms, see Crawley and Paylor 1997). During a certain period, though, they seemed to have lost their priority in animal psychology laboratories to the "rat, which is larger and under certain situations less erratic in its behaviour. The undeclared battle was re-won only recently, with the resurrection of the mouse as the king of the "maze, due to the developments in molecular genetics.
Mice clearly beat rats in the field of genetics. For a mammal, the mouse is an impressive genetic machine. Sophisticated "methods have been developed in recent years for the application of reverse genetics to the mouse, i.e. targeting mutations to identified genes or altering gene dosage ("neurogenetics). These techniques are advancing at a very rapid pace, and the literature is almost overwhelmed with the description and analysis of mutant mice and their "development, physiology, pathology, and behaviour (Blake et al. 1997; Keverne 1997; Silva et al. 1997a; Nelson and Young 1998; Tang et al. 1999; Price et al. 2000; also the Mouse Genome sites on the Web). Furthermore, novel techniques now permit the generation of tissue-, cell type- and temporally restricted gene knockouts (for the particular application to memory research, see Tsien et al. 1996a,b;
Wilson and Tonegawa 1997; Shimizu et al. 2000; also "dementia, "hippocampus, "LTP). These techniques offer considerable advantages to the study of learning and memory, because they could be used to dissociate the effect of a mutation on development from those on behavioural plasticity, and, furthermore, localize the defect to specific brain regions and circuits.
The impressive pace of mouse neurogenetics, and the unavoidable (yet frequently justified) hype, turn it pertinent to pin-point several caveats. First, the novelty and smartness of a research method should not be confused with its usefulness. For example, in certain experiments that aim at establishing the specific role of an identified brain region in a narrow temporal "phase of memory "acquisition, "consolidation, or "retrieval, targeted microinfusion of a selective short-lived drug could be as useful as a knockout. It is also cheaper. Second, almost trivial but sometimes forgotten, careful attention must be devoted to the genetic background of mutant mice, because only if the same background is used, can the difference between the phenotype of the wild type and that of the mutant be ascribed to the mutation rather than the background (Silva et al. 1997b). This is particularly important in the study of behaviour, which, as a rule, is a polygenic trait, hence highly sensitive to modifier genes. Third, those who switch from rats to mice because of the genetic advantages of the latter, should be reminded that mice are not tiny rats. They have their own species-specific physiology and behaviour, and the interpretation of their "performance in learning and memory tasks depends on understanding what is it that the mouse really "perceives and does (e.g. Wolfer et al. 1998). And fourth, behavioural paradigms are not a pH indicator paper. You don't insert a mouse and get a reading. Before deciding on the basis of behavioural tests that a mutant, lesion, or drug has a specific effect on memory, one must carefully evaluate and exclude multiple genetic, developmental, environmental, as well as physiological and behavioural parameters that are not directly relevant to memory. This is not easy (e.g. Deutsch 1993; Gingrich and Hen 2000).
Selected associations: Dementia, Maze, Model, Neuroge-netics, Subject
Was this article helpful?