mutations in the Factor VIII or IX genes (reviewed by Øvlisen et al. 2008 ) and the
Briard with retinitis pigmentosa due to a RPE mutation (Aguirre et al. 1998 ). The
canine genome has also been useful for understanding genetic changes that affect
body shape and size. Chondrodysplasia, the short-legged phenotype typical of
breeds such as dachshund, corgi, and basset hound, has been shown to be due to
an evolutionarily recent retrotransposition of fibroblast growth factor 4 (Parker
et al. 2009 ). A SNP for IGF-1 is likewise associated with the difference in body
size between breeds (Sutter et al. 2007 ). In addition, dogs can be used to study the
genetics of complex traits using both specific breeds and the canine population as a
whole (Parker and Ostrander 2005 ). A good example is the investigation of
cardiovascular disease genes in the dog (Parker et al. 2006 ).
Knowledge of an animal’s genome, and in particular the variation in that
genome, such as the SNPs, has a number of important consequences. Genetic
markers such as specific SNPs can be linked to production traits and aid in struc-
tured breeding programmes in farm animals (e.g. Ibeagha-Awemu et al. 2008 ).
Analysing traits that are economically important to horse owners, such as fertility
and sex determination will be an important consequence of a better understanding
of the equine genome (Chowdhary et al. 2008 ).
3 Use of Transgenic Mice to Reveal Drug Targets
The technology outlined above has been widely used to generate animal models of
the disease and to investigate specific gene function. By comparing normal animals
with animals in which specific genes have been inactivated it has been possible to
elucidate the contribution of a wide variety of genes to various disease processes
and so define specific drug targets with great accuracy. There are numerous
examples of such experiments and the following paragraphs discuss a few specific
examples that demonstrate the importance and utility of this use of genetically
modified animals. In view of the relative ease of ES cell work in mice compared to
other species, together with the cost effectiveness of working with a small mammal
with short reproductive intervals between generations, most of these studies have
been conducted in mice. It should be noted that with standard gene knockouts the
animal develops in the absence of the specific gene function and other genes may
play a substitute role thus confusing interpretation. A good example is the neuro-
peptide Y gene (NPY). This peptide is a potent stimulator of feeding behaviour and
levels fall when animals have been fed ad lib. However, the knockout displays no
abnormal feeding phenotype (Erickson et al. 1996 ). The use of inducible condi-
tional knockouts in which the gene can be inactivated at a precise time and in a
specific tissue by drug activation of a recombinase is in many cases more informa-
tive regarding the effect of acutely blocking specific gene activity, as would be the
case with many pharmacological approaches.
A huge range of mice have been generated as models of human disease and these
can be used to test various therapeutic approaches. However, these models do not
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