University of Wisconsin System
Grant: $416,434 - National Institutes of Health - Sep. 24, 2009
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Award Description: Here we propose direct studies of additional functions of the BMP1-like proteinase, that will be leveraged by use of novel reagents created in this lab, and skills obtained in our previous studies. Specifically, although knockout of the Tll1 gene, which encodes the BMP1-like proteinase, mammalian tolloid-like 1 (mTLL1), is embryonic lethal, we have recently been successful in creating mice with floxed Tll1 alleles, which will allow tissue-specific Tll1 knockout. We've shown that Tll1 is highly expressed in specific structures of the developing and adult central nervous system (CNS). Thus, we've crossed our floxed Tll1 mice to mice in which Cre recombinase is driven by the CNS-specific enhancer sequences of the nestin gene, and demonstrate herein CNS-specific knockout of Tll1. We propose using these mice to determine in vivo Tll1 CNS functions. We request salary support for a lab member to conduct such studies. In addition, we have begun using the powerful zebrafish system to further define functions of the BMP1-like metalloproteinases. However, our previous work in this system employed the equipment and fish of another lab, greatly delaying our studies. We propose acquiring equipment that will enable us to perform zebrafish work in our lab. We propose first using such equipment to determine in vivo roles of the uncharacterized protein zebrafish Chordin-like (zCHL), which we have found to be a maternal factor in earliest embryos, and hypothesize to be a substrate of BMP1-like proteinases, involved in regulating BMP signaling. Obtaining the equipment will not only greatly enhance ability to successfully complete the zCHL study, but will greatly enhance our ability to use the powerful zebrafish system to further explore the BMP1-like proteinases, and ECM components that have also been the focus of research in this laboratory. PUBLIC HEALTH RELEVANCE: We've found that removing a particular gene in mice results in hearts that are in the wrong place, and which don't work sufficiently well to keep the embryo alive. We also have found that this gene is expressed at high levels in the developing and adult central nervous system.
Project Description: See Award Description
Jobs Summary: The University of Wisconsin - Madison appreciates the American Recovery and Reinvestment Act (ARRA) funding. This additional funding will allow the University to retain employees and create new jobs. As of September 30, 2009, no jobs have been created or retained on this award. (Total jobs reported: 0)
Project Status: Not Started
This award's data was last updated on Sep. 24, 2009. Help expand these official descriptions using the wiki below.
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