of U.Va. Health System
Well-bred mice may hold clues to
cause of Crohn's disease
with a naturally occurring bowel inflammation may lead U.Va. researchers
to the cause of Crohns Disease.
Fabio Cominelli, director of the Health
Systems Digestive Health Research Center, has been examining
the mice as part of his effort to track down the cause of Crohns,
a painful inflammatory bowel disease that affects about 1 million
has recently detailed his research with mice in the March issue
of the Journal of Clinical Investigation.
particular mice, a genetically altered colony called SAMP1/Yit
mice, originally came from Tokyo, where researchers found naturally-occurring
lesions while they were researching a skin disease.
were sacrificing the animal when the doctors came across lesions
that looked like Crohns Disease, Cominelli said. We
have done a more elaborate analysis.
has been working with his colony of mice since 1996, performing
additional breeding to sustain the population. He has bred the
mice for 12 generations and he said they are now genetically different
from the mice the Japanese are using.
and his researchers worked on the mice for four years before they
felt they had developed a reliable group. Researchers feared that
by changing the mices environment, there was a risk that
the predisposition to come down with intestinal lesions would
be wiped out.
mice are a particular benefit because Cominelli and his researchers
can study them before they develop the disease, tracking changes
and reactions as the disease progresses. Human subjects, on the
other hand, can not be examined until they already have Crohns.
can also manipulate treatments, environment and genetic and microbiological
conditions in ways that are not possible with humans.
can change the diet, use medications that are not approved for
people, introduce good bacteria into their systems,
Cominelli said. We can do genetic manipulation, study the
effect of the disease on the genes, transfer lymphocytes.
said the mice can be raised in a germ-free environment, then researchers
can experiment by introducing different bacteria.
are remarkable mice because they respond to the same treatments
as human patients, Cominelli said.
patients receive a variety of medications to suppress the inflammatory
response, permitting the tissue to heal, and to treat the symptoms,
which include fever, diarrhea and abdominal pain.
mice have generated a wealth of information for the researchers,
including that the mice respond to antibiotics, Prednisone and
learning a fair amount of stuff, Cominelli said, including
which genes are involved in the process, the role lymphocytes
or immune cells play in causing and mitigating the disease, the
migration of cells in the disease process and which bacteria are
helpful in finding a cure.
find great promise in what we have learned, because while there
has been much progress in understanding some of the mechanisms
involved in intestinal inflammation, using models developed through
chemical or genetic manipulation, there remains a need of a model
that displays the complexities specific to Crohns Disease,
spontaneous model that can be used to further study Crohns
disease in humans is significant. When combined with the remarkable
resemblance of the mice lesions to human Crohns disease
and similarities in associated immune responses, this model is
a unique tool for pursuing the cause, and eventual cure, for this
disease, he added.
received a $5.1 million, five-year grant from National Institutes
of Health in September 2000 to study Crohns Disease. This
funds the work of 25 people, including eight to 10 investigators,
technicians, post-doctoral fellows and 1,000 to 1,500 mice, which
cost about $100,000 a year to maintain.