ABSTRACT
This chapter discusses the rapidly evolving area of genetically modified
mouse models and their application to the understanding of basic mechanisms of lung injury and repair. The development of methods to manipulate
the mammalian genome has provided significant opportunities for the
advancement of basic science research, agriculture, and biotechnology. As
described in this chapter, genetically modified mice are variants of the spe-
cies generated through introduction of stable genetic alterations into germ-
line DNA. These alterations may either result from the random insertion of
new DNA sequences, known as transgenes, or the introduction of site-
specific insertions and=or deletions. Genetically altered mice provide a unique tool allowing researchers to bridge the gap between carefully
designed in vitro studies and classical in vivo models. Current state-of-
the-art approaches in the development of transgenic and knockout mouse
models allow precise dissection of gene function in the context of the most
complicated of biological systems, the whole animal. However, a number of
factors including the design of transgenes and targeting vectors, screening of
founder mice, and variations in background can significantly impact the
phenotype associated with a genetic modification. It is essential to take these
factors into account in developing and utilizing transgenic mouse models in
basic research. Due to the importance of experimental and genetic charac-
terizations in establishing mouse models, the first half of this chapter summarizes selected approaches relevant for subsequent interpretation of
phenotype [technical details for producing transgenic mice are not empha-
sized due to their in-depth coverage in other published texts (e.g., see Refs.
1, 2)]. The latter half of the chapter focuses on the use of specific genetically
modified mouse models in analyzing mechanisms of lung injury and repair.
Further discussion of cell and animal models used in studying lung injury
and inhalation toxicology is provided in Chapters 10 and 12.
