Abstract
Gene manipulation by disrupting important genes using homologous recombination in mammals has provided important insights into their function and development with regard to disease. However, many questions related to the genetic pathways that regulate cellular differentiation and function remain to be clarified. In particular, analysis of genetic pathways that control embryonic skeletal development is often hindered by the disruption of critical genes that function in early embryogenesis, thereby leading to embryonic or perinatal death and thus preventing study of the role of these genes in skeletal development and physiology postnatally. To overcome this problem gene-targeting methods, using site- and time-specific recombination based methods with the Cre/loxP system, have been used to delete particular genes in specific tissues and stages during development. Thus, the generation and characterization of transgenic mice expressing Cre recombinase, under the control of a tissue-specific and stage-specific promoter, has become prerequisite for study of the physiology and homeostasis of specific tissues during a specific time frame. In this report, we introduce the principles and methods of site-specific and time-specific recombination using the Cre/loxP and inducible Cre system, and discuss the potential applications for applying this system to the study of the development and physiology of the skeletal system.
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