Transgenic Mouse Technology in Skin Biology : Generation of Knockin Mice

INTRODUCTION Genetic modification of model organisms is a powerful tool to study human diseases in vivo. Mice have become the main subject of interest for basic researchers because they share a broad spectrum of physiological and pathological similarities with humans. These similarities, genetic accessibility, and a defined genetic background within the laboratory mouse strains provide the basis to analyze in vivo cellular and molecular pathways that are altered in human diseases. Knockout and knockin mice have become valuable tools to investigate the role of certain proteins and thereby have helped researchers to overcome cause and consequence problems arising from biochemical data (Hacking, 2008). For biomedical research, the knockin mouse opened the possibility of studying the in vivo pathological consequences of gene mutations associated with human disease and examining their similarity to human pathologies. Whereas knockout technology aims to delete a gene or part of a gene, knockin technology introduces specific mutations or cDNAs into a known locus of the genome. The altered mice can then be used to study the molecular mechanisms by which specific mutations can contribute to human diseases. Examples of the potential of knockin technology are the introduction into mice of human orthologs—the human equivalent of the mouse gene—and investigation into how either single-point mutations or gene insertions/deletions/inversions observed in human disease affect gene function. In addition, knockin technology can be used to introduce reporter genes under the control of a cell type–specific promoter to follow their fate over time in a defined location within the genome (Vorhagen et al., in press). An important advantage of knockin technology as compared with integration by chance (random integration) is its directed integration into a known locus in the genome. By contrast, random integration can result in multiple-copy integration and/or disturbance of genes where the transgene was inserted. For example, random integration may occur in the promoter of another gene, resulting in disturbed transcription of that gene.