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 (http://www.hgsc.bcm.tmc.edu/), 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
(http://www.mcw.edu/pathol/ed/), 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
http://gateways.bmn.com/magazine/article?pii=S1359644604031289

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