World's lab mice may have Japanese roots

Laboratory mice used in research to discover the mechanisms that cause disease and to develop medicines were first bred on the east coast of the United States more than 100 years ago.

Using a supercomputer, researchers at the National Institute of Genetics (NIG) based in Mishima, Shizuoka Prefecture, and other entities compared the genetic code of lab mice with other mice, and found there is a great possibility their ancestors were Japanese mice that had been taken to Europe in the Edo period (1603-1867).

According to Toshihiko Shiroishi, 61, NIG vice director general, there are currently around 400 strains of lab mice used for different research purposes.

Such mice were sourced, at around the turn of the 19th century, from mice provided by a woman teaching at a primary school near Boston in the United States, who kept about 1,000 mice as pets.

The mice bred by the teacher were believed to be from western Europe, but about 10 years ago, a US research group investigating the genes of lab mice reported that some of the genes originated from Asian mice.

Later research discovered that among the genes of Asian mice, those found in the lab mice originated from small Japanese mice.

Why are the genes of lab mice bred from mice brought from Europe to the United States mixed with the genes of Japanese mice? Shiroishi set out to unravel this mystery with the cooperation of RIKEN.

One hint was found in British documents that describe Japanese mice being brought to Europe by traders in the late Edo period. Woodblock print artists working in the Edo period, such as Katsushika Hokusai, made many images of mice, and they were reputed to be popular pets among townsfolk of the period.

In the middle of the Edo period, a book on breeding mice called "Chingan Sodategusa" was published. This book contains many pictures of a small type of mouse called "mamebuchi," with black spots on its white coat.

Shiroishi's research team focused on the panda mouse, a type which closely resembles the mamebuchi. The variety was found in a pet shop in Denmark around 30 years ago by former Prof. Kazuo Moriwaki of NIG, who died last year.

Moriwake received the panda mouse from an acquaintance, and he named the strain bred from its offspring "JF1," raising them at NIG.

The research team decoded the genomes of JF1 as well as a type of mouse caught in Mishima called "MSM," and compared the gene sequences using a supercomputer.

As a result, the team discovered they were 99.99 per cent similar, and that the JF1 strain, the forebears of which had been sold in Denmark, are, when examined genetically, Japanese mice.

The genome of the C57BL/6, a common strain of lab mice bred about 100 years ago, has already been decoded. When the research team used a supercomputer to compare the gene sequences of the JF1 with those of the C57BL/6, there were parts of the C57BL/6 gene sequences that matched the JF1 exactly.

From the analysis of the genomes and the documentary evidence, Shiroishi said, "There is a possibility that the ancestors of the JF1 strain were mamebuchi taken from Japan to western Europe."

Other alternatives

"Mice are small, easy to breed and very fertile. Because they are mammals like humans and close to us genetically, they are indispensable for medical and scientific research," says Prof. Shigeru Kyuwa, 58, of the University of Tokyo's Laboratory Animal Research Center, about the significance of lab mice.

There are a number of other animals used in research. Rats, guinea pigs, pigs, monkeys, chickens, newts, killifish and silkworms are all used depending on the purpose of the research.

From an animal protection perspective, when performing experiments on animals, the animal welfare and management law and other regulations require that the animals' pain be minimized and the number of experiments be reduced as much as possible.

In recent years, there have been efforts to replace laboratory animals, such as by using human cells or running simulations on computers. "It is important to have feelings of caring and gratitude toward laboratory animals," Kyuwa said.