Target Discovery and Validation Reviews and Protocols

10
Transgenic Animal Models in Biomedical Research
Louis-Marie Houdebine
Summary
Transgenic animals have become a key tool in functional genomics to generate models for
human diseases and validate new drugs. Transgenesis includes the addition of foreign genetic
information to animals and specific inhibition of endogenous gene expression. Recently, animal
models provided novel insight and significantly improved our understanding of the initiation and
perpetuation of human diseases. Moreover, they are an invaluable tool for target discovery, validation,
and production of therapeutic proteins. However, despite the generation of several transgenic
and knockout models, obtaining relevant models still faces several theoretical and technical
challenges. Indeed, genes of interest are not always available and gene addition or inactivation
sometimes does not allow clear conclusions because of the intrinsic complexity of living organisms
or the redundancy of some metabolic pathways. In addition to homologous recombination,
endogenous gene expression can be specifically inhibited using several mechanisms such as RNA
interference. Here, some animal models are described to illustrate their importance in biomedical
research. Moreover, guidelines for generation of these animals are presented.
Key Words: Diseases; models; pharmaceuticals; transgenic animals.
1. Introduction
One of the main aims of modern biology is to identify and characterize the function
of vertebrate genes. Approximately 30 yr ago, it became possible to clone and
investigate the function of most abundantly expressed genes. The discovery of
microsatellite sequences and the complete sequencing of the genome of some
species, namely, mice, have facilitated the identification of genes involved in
human diseases. For example, correlations between the sequence of microsatellites
and other genetic markers in the same family members with cystic fibrosis led to
the identification of the cystic fibrosis transmembrane conductance regulator
(CFTR) gene and mutations that are causing the disease in question. Moreover,
From: Methods in Molecular Biology, vol. 360, Target Discovery and Validation Reviews and Protocols
Volume I, Emerging Strategies for Targets and Biomarker Discovery
Edited by: M. Sioud © Humana Press Inc., Totowa, NJ
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