Gene targeting of Cdh1 and Emi1 in mice

Abstract

Cell cycle progression is mediated by oscillation of cyclin-dependent kinase (Cdk) activity. Cyclins constitute the regulatory subunits which provide substrate specificity for their associated Cdks. Cdhl and Cdc20 regulates anaphase-promoting complex (APC) for Cdk activity in cell cycle progression. Cdhl-dependent APC (APC-Cdhl) activity targets mitotic cyclins from the end of mitosis to the G1 phase. Emi 1 promotes mitotic entry by inhibiting the APC-Cdc20 activity, and also promotes S phase entry inhibiting APC-Cdhl activity. These protein activities are tightly regulated for genomic integrity. In addition, Cdhl is dispensable for viability and cell cycle progression in yeast and chicken cells. However, functions of Cdhl and Emi 1, a regulator of Cdhl are poorly understood in living organism. To better understand the functions of Cdhl and Emil in living organisms, an attempt was made to generate Cdhl knockout mice and Emil knockout mice in this study. So far, a successful attempt was made to generate Cdhl and Emil chimeric mice. Although knockout mice are not available at present, Cdhl 4" mice and mice are soon to be generated. These mice will be useful to understand functions of Cdhl and Emil for cell cycle regulation and chromosome instability leading to tumor development in living organisms.