This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a pilot proposal requesting funds to support collaborative research between three RCMI investigators with shared research interests. A central theme of the proposal is the use of mouse gene knockout studies to gain insights into the role of important signaling pathways during development. Gene disruption provides a powerful tool towards understanding complex biological processes. Transgenic mouse lines carrying single mutations in genes of interest will be generated using a new highly efficient Targeted gene trapping technique. These knockout lines will be used by each of the three investigators. The focus of the current research proposal will be to examine the role of Wnt signaling pathway during development. A mouse knockout line for the Kremen1, a gene which encodes an inhibitory receptor for the Wnt signaling pathway, has already been established and the initial studies will focus on phenotypic analyses of these mutant lines. Utilizing these krm1 mutants, the three investigators will test the basic hypothesis that loss of Krm1 function results in increased Wnt signaling leading to the following aberrant pathways: 1) retinal vascular development, 2) T cell development and 3) B cell development. Because of the expense of generating mouse knockouts, this is a very efficient and economical approach of sharing resources and promoting collaboration among RCMI investigators. It is expected that the results from the pilot project will be the basis of new research grants and contribute significantly towards the overall goals of the RCMI.
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