Ask any scientist, and he'll tell you who the top dog in the laboratory is today:

It's the mouse.

In less than a century, these rodents have managed to go from pest to pet research subject, with more than 25 million used in labs around the world. How they managed it is a tale that involves a retired schoolteacher, a descendant of Paul Revere, two auto industry barons -- plus a bit of animal incest.

It all starts in 1900 with Abbie E.C. Lathrop of Granby, Mass. Lathrop was a 32-year-old former schoolteacher who had moved to Granby around that time with the notion of starting a poultry farm. That soon flopped, and she switched from chickens to rodents, hoping to cash in on the Victorian craze for "fancy" mice.

Fancy mice are pets whose roots go back to 17th-century Asia, where breeders began to select and breed unusual-looking mutant mice. A Japanese book, Chingan Sodategusa, detailed popular early breeds -- the albino, dwarf and waltzing mouse (so named because the mouse appeared to dance, a behavior, scientists later learned, that stemmed from an inherited inner-ear defect).

By Lathrop's day, the fancy-mice boom had spread to Britain and New England. Lathrop started small.

"She started with a single pair," reported the Springfield Sunday Republican in a 1913 feature story on her. (Eventually, her barn and sheds would hold more than 11,000 mice, which she kept in straw-filled boxes and fed crackers and oats.)

Orders started pouring in -- for creamy buffs, rare ruby-eyed yellows, white English sables, red creams and other popular fancy breeds. Then, in 1902, Lathrop received an unusual order -- not from a fancier but a Harvard University zoologist named William Castle. His name is all but forgotten today, but Castle was then at the forefront of the new field of genetics.

Moravian monk Gregor Mendel and his groundbreaking experiments on pea plants had just been rediscovered. Scientists such as Castle, notes Princeton University biologist Lee Silver, were curious whether the genetic laws Mendel had worked out on plants also held true for more complex organisms such as mammals. If so, experiments with these animals would presumably say something about humans.

Castle turned to mice. Newborn pups take only about 10 weeks to mature, so scientists could breed several generations in no time. Fancy mice were also small, tame and required less space than dogs or other animals. Most important, fancy mice were a physically diverse lot.

Though they are not as diverse as cats and dogs, breeding over the centuries had transformed common field mice into a quirky collection of creatures. Fancy mice came in black, blue, silver, champagne, red, lilac and white. Their hair could be short, long, curly or frizzy, or they could be bald. Some had huge ears that stuck out like handlebars. Others, such as waltzing mice, had unusual behavioral traits.

For early geneticists, who could not yet peer inside the creature's DNA to see what was going on, this made the mice ideal -- they could visually observe the results of their genetic experiments. Castle was not the only one to realize this.

Lathrop soon "had orders for mice by the hundreds coming from research laboratories as far away as St. Louis and New York," notes Herbert Morse in Origins of Inbred Mice. Suddenly the mouse had a tiny toehold in the laboratory -- which, says historian Karen Rader, stemmed from being at the right place at the right time.

"Or the wrong place, depending on whose perspective you're looking at," says Rader, who teaches at Sarah Lawrence College and is writing the first comprehensive history of the laboratory mouse for the Princeton University Press.

Before Castle, the mouse had not been entirely alien to the laboratory.

British physicist Robert Boyle and his assistant, Robert Hooke, in the 1660s reputedly trapped mice under a glass and slowly pumped out the air to learn more about the properties of air. A century later, their compatriot Joseph Priestley conducted similar experiments that led to the discovery of oxygen.

But Victorian-age biologists were dabbling with many animals -- including guinea pigs, fruit flies, dogs and rats. The mouse was still in the minority. The man who would ultimately solidify its scientific fate was one of Castle's undergraduate students, Clarence Cook Little.

A great-great-grandson of silversmith and Revolutionary War patriot Paul Revere, Little was the son of an accomplished dog breeder who as a child raised canines as well as mice, guinea pigs and pigeons. After entering Harvard in 1906, Little enrolled in one of Castle's genetics classes. When the revered zoologist "skidded a live mouse to him across the bench top and instructed him to learn everything about it," Little was hooked, writes Rader.

After conducting two genetic mouse studies as a warm-up, Little, who was known as the "mouse man" among Castle's students, began an experiment that would lead to the creation of the modern lab mouse.

Little's innovation was the "inbred strain." By mating brother to sister over and over, he created rodents that were genetically alike.

In fact, after 20 generations the mice were nearly 99 percent identical. In 1909 he created the first inbred strain, dba, which is still used in research. Before inbred strains, scientists couldn't say for certain whether their results were because of the genetic quirks of a particular mouse or the experiments.

Genetically identical strains also ensured that experiments could be repeated in different laboratories by different scientists with different mice. The inbred strain essentially gave geneticists a fuzzy test tube for their work, Rader says.

But Little wasn't done yet. After receiving his doctorate, he left Harvard and moved on to stints in research and administration at various institutions.

In 1929 Little persuaded auto industry tycoons Edsel Ford (son of Henry) and Roscoe Jackson, chief of Hudson Motorcar Co., to finance an independent research facility, Jackson Laboratory, near one of their favorite vacation spots, Bar Harbor, Maine. Mouse research bloomed.

Before long, scientists at Jackson and elsewhere were making and studying cancer-riddled mice, alcoholic mice and fat mice. Once the ability to manipulate DNA was developed in the 1970s, they made diabetic mice and mice with glaucoma and dozens of other diseases to gain insight into human diseases.

The Jackson inventory eventually made lines nicknamed deaf waddler, claw paw, flailer, twitcher, grizzled, greasy, loop tail, stargazer and hundreds of others. Today the laboratory houses nearly 2,500 genetically distinct strains. It sold 1.9 million mice to researchers last year.

Ultimately, says Rader, it was as much Little's personality as his science that helped the mouse's cause. In the early days of Jackson Lab, he started the "Mouse Club of America" to ensure a supply for scientists.

Little, who died in 1971, once even wrote to Walt Disney to propose mutually beneficial PR, because his mice and Mickey were surely related.

"He had a certain evangelism about him," says Rader. "He really believed you couldn't do an experiment without experimenting on the mouse."