Target Discovery and Validation Reviews and Protocols

164 Houdebine
Fig. 1. Different methods to isolate genes and the contribution of transgenesis in
gene study and use.
forwards genetics using the chemical mutagen ethylnitrosourea to produce random
mouse mutations identified several genes, some of which have been correlated
with the obtained phenotype. Then, the mutated genes were identified and characterized
(1). Recently, the systematic sequencing of genomes and expressed
sequence tags has facilitated the identification of most genes (Fig. 1). However, the
functions of most of the predicted human genes are not yet known.
Once a gene is identified, it can be used for several applications (Fig. 1): for
example, discovery of alleles and mutants, study of gene expression mechanisms,
embryo selection in humans, animal selection, production of the corresponding
protein, gene therapy, and biotechnological applications implementing transgenesis
(see Chapter 11, Volume 1). These postgenomic approaches, which reconcile
physiology and molecular biology, are one of the major challenges for biologists.
Transgenesis is one of the major tools of postgenomics. This technique is being
used to produce recombinant protein in milk (2) to adapt pig organs to human
recipients (3), and to improve animal production (4). Yet, at least 95% of transgenic
animals are being generated to study gene function and mechanisms as well as to
create models for the study of human diseases and the validation of new drugs.
The first transgenic animals, mice, were obtained in 1980 by using DNA
microinjection into embryo pronuclei. Two years later, it was shown with the