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STUDYING mouse skulls might give scientists important clues about early
stages of the developmental defects that cause Down’s syndrome.

People with Down’s syndrome have inherited an extra copy of all or part of
chromosome 21, usually from their mother. It’s the most common genetic cause of
learning difficulties, occurring in about 1 in 700 live births in the Western
world. People with Down’s develop characteristic facial features and carry a
higher than normal risk of heart and immune system defects.

Roger Reeves of Johns Hopkins University in Baltimore, Maryland, is
pioneering research in a similar disease in mice that have been genetically
altered to have an extra segment of chromosome 16—the mouse equivalent of
human chromosome 21. This gives them characteristics of the human disease,
including cognitive problems.

But Reeves is eager to track the earliest signs of Down’s syndrome, which
start during embryonic development. “And it isn’t easy to give the mouse a
cognitive test before birth,” he says.

So Reeves and his colleagues decided to look at how mouse skulls develop.
They used a laser microscope to produce three-dimensional scans of skulls from
the engineered Down’s mice and normal animals. They then fed the scans to a
computer program that generated models of the skulls.

When they compared adult mouse and human skulls they found that the bones are
shorter front-to-back and longer side-to-side in both the engineered mice and
people with Down’s.

Reeves says this is further evidence that the mouse model accurately reflects
the human syndrome. And by measuring the skulls in engineered mouse embryos in
the early stages, he might be able to link the activity of certain genes on the
extra chromosome to the onset of Down’s. “Then we can start thinking about how
to intervene against these factors,” he says.