Embracing the rat
Stephani Sutherland
Drug Discovery Today 2004, 9:468
In the past fifty years, the role of the rat has shifted
from a bane on society - eater of harvests, carrier of
disease - to an animal of great utility, as the best
physiological model for research. Now the rat's value to
researchers is poised to skyrocket with the recently
completed sequencing of the rat genome. Richard Gibbs,
Director of the Human Genome Sequencing Center at Baylor
College of Medicine (hgsc.bcm.tmc.eduhgsc.bcm.tmc.eduOpen ↗), headed
up the enormous consortium of researchers from over 20
institutions worldwide. Gibbs says that the sequence will
be valuable to many areas of biology, but its greatest
potential lies in the development of models of complex
human disease.
An ideal model for complex disease
The mouse has been a favorite tool of geneticists. Knock-out
technology has allowed them to insert or delete individual
genes in mice, providing a useful model for mendelian
disease. The difficulty with manipulation of rat genes,
though, has been 'the Achilles heel for rat in genetics,'
says Gibbs. But the rat has been the darling of
physiologists. Allen Cowley, Jr, Chair of the Physiology
Department at the Medical College of Wisconsin
(mcw.eduedOpen ↗), points out that the rat's
size has allowed for 'meaningful physiological organ and
whole animal studies,' which has made them such a valuable
animal model.
Cowley, who was not involved in the sequencing project, sees
great potential for the rat genome in disease research. 'The
mouse has been of tremendous use, but not for complex
diseases.' The rat, in contrast, has been bred into hundreds
of model strains for diseases like diabetes, cardiac
disease, and obesity. For example, notes Cowley, there are
over a dozen rat models for hypertension alone, each of
which represents the biology of some portion of the human
disease population. Researchers have used these rat models
to identify large regions of a chromosome-or quantitative
trait loci-that contribute to a condition. When it comes to
quantitative genetics, says Gibbs, 'the rat really has such
a huge head start.' But the individual genes that contribute
to a disease are in most cases unknown. The genome sequence
will allow one to 'straight away go to the rat and look at
the orthologues' to human disease genes. Cowley too is
enthusiastic that the genome will 'simplify the search for
genes in complex disease.' Both are hoping that the improved
rat model of disease will eventually lead to better
therapeutic targets, and lower the current 90% failure rate
in drug development.
Read the rest at BioMedNet gateways.bmn.commagazineOpen ↗
/article?pii=S1359644604031289
Posted by Robert Karl Stonjek.