Keratin-dependent regulation of protein biosynthesis and cytoskeletal organization during epithelial differentiation

点击翻译按钮获取中文摘要

Keratins belong to two protein families with 54 members, expressed from the blastocyst stage onwards in a tissue-specific fashion. The provide mechanical integrity to epithelia and are scaffolds for cell signaling proteins, but, like for other multigene family members, the function of individual proteins has not been resolved. The fact that all keratin genes, unlike members of many other gene families, are clustered in two contigs on chromosomes 11 and 15 in the mouse, offers a unique approach to address the above problem. We have started to use the cre/lox system to delete the type I and type II keratin gene clusters to generate true keratin null mice, a prerequisite for transgenic rescue experiments. This classical approach of gene deletion/gene replacement was instrumental for the understanding of developmental processes in other model organisms, eg. Drosophila melanogaster. In the first phase of this project we focus on the role of keratins in mouse embryonic development and ask whether a single keratin pair of embryonic or epidermal origin supports normal development in the absence of all other keratins. This will reveal whether epidermal keratins can fulfill both structural and signalling functions typical of simple epithelial keratins. The proposed study will provide important insights into type-specific keratin function and is of general significance for tissue-specific functions of other large gene families.