What is a mouse? Ask any small child and you will hear the answer a small furry creature with big ears and a big smile. Today, in Japan, Europe, America, and elsewhere, this question evokes images of that quintessential mouse icon Mickey; but even before the age of cinema, television, and theme parks, mice had entered the cultures of most people. In the English-speaking world, they have come down through the ages in the form of nursery rhymes sung to young children including "Three blind mice" and "Hickory, dickory dock, the mouse ran up the clock...." Artistic renditions of mice in the form of trinkets, such as those shown in Figure 1.1 and on the cover of this book, are sold in shops throughout the world. Why has the mouse been in the minds of people for so long? The most obvious reason is that one particular type of mouse the so-called house mouse has lived in close association with most, if not all, human populations since the dawn of civilization.
This dawn occurred at the end of the last ice age, some 10,000 years ago, across a region retrospectively called the Fertile Crescent that extends from modern-day Israel up through Lebanon and Syria and curves back down through Iraq toward the Persian Gulf (Figure 1.2). It was in this region at this time known as the neolithic transition that tribes of nomadic hunters and gatherers began to cultivate plants and domesticate animals as a means for sustenance (Ammerman and Cavalli-Sforza, 1984). Farming eliminated the need for constant migration and brought about the formation of villages and the construction of permanent shelters for both people and their livestock. With the seasonal planting of crops, families needed to store dry food, in the form of grain, for both themselves and their animals. With food reserves in granaries and cupboards, the house mouse began its long interwoven history with humankind.
The ancestors of the house mouse, who were concentrated in the steppes of present-day Pakistan at that time (Figure 1.2), had been living happily oblivious to people for eons, but suddenly (in terms of evolutionary time), migrants to the new Neolithic villages found mouse paradise in the form of a secure shelter with unlimited food (Auffray et al., 1990). With their ability to squeeze through the tiniest of holes adults can pass through apertures as small as a single centimeter in width (Rowe, 1981) our furry friends were clearly pre-adapted to take advantage of these Neolithic edifices, and with their agility and speed, they were able to stay one step ahead of the cleaver wielded by the farmer's wife. This pre-adaptation, and the opportunistic ability to eat almost anything, has allowed the house mouse to become the second most successful mammalian species living on earth today (Berry, 1981; Sage, 1981). 1
When people wandered out from the Middle East in search of new lands to
cultivate, mice followed as stowaways within the vehicles used to carry household
belongings. Later, they would travel with ship-borne merchants going to and from
distant lands. In this millennium, it is not too farfetched to imagine mice traveling
on the Santa Maria with Columbus to the new world, and on horse-drawn buggies
with families emigrating from the original American colonies to the Western part
of the continent. As people overcame harsh environments through the
construction of artificial habitats, these became the natural environment for the
house mouse. Freeloading on people has allowed the house mouse to enjoy a
wider range than all species but one. Today, house mice can be found wherever
there are permanent populations of people (as well as many places where there are
none), in both urban and rural areas, on all of the continents, at altitudes as high as
15,600 feet (4750 m), as far north as the Bering Sea and as far south as sub-Antarctic islands
(Berry and Peters, 1975;
Although mice and farmers may not have seen eye-to-eye, one can imagine the potential for a very different type of relationship between mice and people not directly affected by their dastardly deeds. This is because mice are often viewed in a very different light than other animals as best summed up in the words of a contemporary artist:
The mouse is a great friend to artists, then, because we like him. He doesn't seem to have any specially bad characteristics at worst, his life is a little drab, but we all suspect our lives of being just that... Not enough like us to unnerve us, he is a tiny creature (therefore clearly inferior) who looks up to us and fears us (therefore reassuring), who is not directly useful to us (therefore not a menial), and can be a pleasant furry companion without making extensive demands on us (therefore a true friend). No wonder artists appreciate the mouse; put him in a work and you win your human audience instantly... ( Feingold, 1980)
The house mouse was highly visible to children growing up on farms as well as in towns, and legend has it that the tame animals wandering in and out of Walt Disney's original cartoon studio in Kansas provided the inspiration for the creation of Mickey Mouse (Updike, 1991). House mice can express a high level of interesting activity in a small amount of space when presented with various playthings. They can breed easily in captivity, their diets are simply satisfied, they can be housed in small spaces, and one can select artificially for increased docility in each generation. With continuous human contact from birth, mice acclimate to touch and can be handled quite readily.
Early instances of mouse domestication, and even worship, by the ancient Greeks and Romans is described in detail by Keeler (1931). From the classical period onward, the domesticated mouse has appeared in various Eurasian cultures. Of particular importance to the history of the laboratory mouse was the fondness held for unusual-looking mice by the Chinese and Japanese. This fondness led Asian breeders to select and develop a variety of mutant lines with strikingly different coat colors, some of which can be seen in detailed paintings from the eighteenth and nineteenth centuries. During the nineteenth century, the house mouse became "an object of fancy" in Europe as well (Sage, 1981), and British, Chinese, and Japanese traders brought animals back and forth to develop new breeds. By the beginning of the twentieth century, European and American fanciers were familiar with lines of mice having fanciful names like white English sable, creamy buff, red cream, and ruby-eyed yellow (Sage, 1981).
A critical link between the mouse fanciers and early American mouse geneticists was Miss Abbie Lathrop, a retired school teacher who began, around 1900, to breed mice for sale as pets from her home in Granby, Massachusetts (Morse, 1978). Conveniently, Lathrop's home and farm were located near to the Bussey Institute directed by William Castle of Harvard University (see Section 1.2.2). Not only did Lathrop provide early mouse geneticists including Castle and his colleagues at Harvard and Leo Loeb at the University of Pennsylvania with a constant source of different fancy mice for their experiments, but she conducted her own experimental program as well with as many as 11,000 animals breeding on her farm at any one time between 1910 and her death in 1918 (Morse, 1978). Many of the common inbred lines so important to mouse geneticists today including C57BL/6 and C57BL/10 (commonly abbreviated as B6 and B10) are derived entirely from animals provided by Abbie Lathrop. A more detailed account of her contributions along with photographs of her breeding records and her farm can be found in a historical review by Morse (1978).