chapter  14
An Inducible and Reversible Mouse Genetic Rescue System
ByHongkui Zeng, Kyoji Horie, Linda Madisen, Maria N. Pavlova
Pages 23

Introduction In the post-genome era, a major challenge is deciphering the function of thousands of newly identied genes. One of the main approaches for studying gene function involves inactivation of genes in cells or animals using random (chemical or insertional) mutagenesis or gene targeting. A common problem with these methods stems from the fact that the gene of interest is usually mutated throughout the animal’s life. As a result, 1) in many cases the mutation leads to embryonic or neonatal lethality, precluding the assessment of the gene’s function in later life; 2) in viable mutants interpretation of observed phenotypes is often complicated by the inability to distinguish the direct eects of the gene loss at the time of observation from the results of developmental abnormalities caused by the gene loss earlier in life; 3) in still other cases, life-long absence of a gene product causes compensatory adjustments of activities of other genes precluding the elucidation of the function of the gene of interest. Conditional knockout and gene expression technologies, such as the Cre/lox-mediated tissue-specic knockout [1] and the tetracycline (Tet) regulated transcriptional activation system [2], can regulate gene expression in a more spatially and temporally controlled fashion. However, these technologies are often laborious to establish and the results are frequently variable.