The purpose of the Animal Core of this Program Project is to support the four research projects by maintaining and breeding mice, collecting cells, tissues and blood from mice, performing bacterial infection with Porphyromonas gingivalis and Chlamydia pneumoniae, and performing in vivo imaging studies by MRI / MRA. To define cell specificity of IL-lp signaling in the development of inflammatory atherosclerotic plaque, the Animal Core will perform bone marrow transplantation to produce bone marrow chimeric mice in which either the donor cells or the recipient mice are IL-1p KO, and challenge these mice with C. pneumoniae or P. gingivalis. The Animal Core will generate two novel transgenic mice, in which TLR2 or IL-1 receptor (IL- 1R) expression is targeted specifically to endothelial cells. These mice will be used to examine endothelial cell TLR2 or IL-IR signaling in inflammatory responses to P. gingivalis and C. pneumoniae infection. We currently maintain some of these KO mice in our mouse colony, including the ApoE, TLR2, IL-1 R single KO mice as well as ApoE/TLR2 double KO mice. We will obtain IL-ip, LXRa, LXRp single KO mice, and LXRa/p double KO mice.We will cross KO mice to generate double KO mice: ApoE x LXRa, ApoE x LXRp, ApoE X IL-IR, and ApoE x IL-1 p. To support the four Projects of the Program, we propose the following Aims for the Animal Core:
AIM 1. Maintain and breed knockout mouse lines.
AIM 2. Obtain cell, tissue and blood samples from mice for analysis by each project.
AIM 3. Perform infection of P. gingivalis or C. pneumoniae, generate bone marrow chimeric mice by bone marrow transplantation, and perform MRI / MRA for each project.
AIM 4. Construct novel transgenic mice strains in which TLR2 or IL-IR expression is targeted to endothelial cells.
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