The "tail short" mutant mouse was first discovered in 1946 among a litter of offspring born to a highly inbred strain of mice raised in a breeding program at the National Cancer Institute in Bethesda. The mutant mice all had very unusual skeletal features: short, stubby tails and an extra set of ribs in their neck vertebrae - but for years no one knew why.

As described in this week's issue of the journal Cell, UCSF Faculty Fellow Maria Barna, PhD, and colleagues, reveal the secrets of this mutant mouse, and in the process have identified a molecular machine called the ribosome as the factor that exerts a new control over gene expression.

When the first tail short mice were produced, doctors recognized the uniqueness and potential importance of the mouse immediately. It wasn't just that the skeleton was malformed – it seemed to be misplaced. The neck vertebrae had ribs and resembled vertebrae lower in the spine. It was as if the body plan of this mouse had been incorrectly mixed up in early development, though it was beyond the ability of scientists in those days to determine why.

Through the decades, the mouse remained a curiosity of sorts. Its progeny were carefully bred year after year, but decades passed before anyone could determine which genes were responsible for its unusual features.

Finally, a few years ago, Barna and her colleagues, became interested in the mouse, and she worked with scientists at the National Institute of Genetics in Japan to identify the exact mutations that cause the malformations. A developmental biologist herself, Barna suspected that the mouse's peculiar skeletal structures suggested some sort of anomalous "patterning" in early development, where one part of the body forms incorrectly in the shape of a different part. What they found, said Barna, was a complete surprise.

The mutations turned out to be in the ribosome, a massive molecular machine that makes proteins and are common to all forms of life. They can be found in every cell in every tissue of the human body, and scientists believe that similar versions have been inside every cell of every creature that ever lived – whether cat, carp, cholera or Caesar.

The ribosome is so common because it plays a central role in biology by making proteins that do everything from building the body's tissues to carrying out crucial biological functions, like breaking down food in the gut and encoding memories in the brain. Despite its importance, scientists had always assumed that the ribosome was something of an automaton -- a machine that simply took instructions from a creature's genetic code and spit out proteins. Mutations in the tail short mouse, however, showed otherwise.

This discovery has broad implications for how we think about developmental biology, and it may explain the origins of numerous developmental diseases. It also may help suggest new ways of treating certain types of cancer, many of which may be linked, at least in part, to problems in how the body regulates gene expression.

"The ultimate outcome of gene expression is the production of proteins," said UCSF Faculty Fellow Maria Barna, PhD, who led the research. "Our study suggests that there is a new way of controlling which types of proteins will be produced in which types of cells."

For more details, please read the official release at UCSF.