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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|Huang, Nasi; Gibson 3rd, Frank C (2014) Immuno-pathogenesis of Periodontal Disease: Current and Emerging Paradigms. Curr Oral Health Rep 1:124-132|
|Koupenova, Milka; Vitseva, Olga; MacKay, Christopher R et al. (2014) Platelet-TLR7 mediates host survival and platelet count during viral infection in the absence of platelet-dependent thrombosis. Blood 124:791-802|
|Shaik-Dasthagirisaheb, Yazdani B; Huang, Nasi; Gibson 3rd, Frank C (2014) Inflammatory response to Porphyromonas gingivalis partially requires interferon regulatory factor (IRF) 3. Innate Immun 20:312-9|
|Beaulieu, Lea M; Lin, Elaine; Mick, Eric et al. (2014) Interleukin 1 receptor 1 and interleukin 1? regulate megakaryocyte maturation, platelet activation, and transcript profile during inflammation in mice and humans. Arterioscler Thromb Vasc Biol 34:552-64|
|Clancy, Lauren; Freedman, Jane E (2014) New paradigms in thrombosis: novel mediators and biomarkers platelet RNA transfer. J Thromb Thrombolysis 37:12-6|
|Freedman, Jane E (2014) Inherited dysfunctional nitric oxide signaling and the pathobiology of atherothrombotic disease. Circ Res 114:1372-3|
|He, Xianbao; Berland, Robert; Mekasha, Samrawit et al. (2013) The sst1 resistance locus regulates evasion of type I interferon signaling by Chlamydia pneumoniae as a disease tolerance mechanism. PLoS Pathog 9:e1003569|
|Freedman, Jane E; Tanriverdi, Kahraman (2013) Defining miRNA targets: balancing simplicity with complexity. Circulation 127:2075-7|
|Shaik-Dasthagirisaheb, Y B; Huang, N; Baer, M T et al. (2013) Role of MyD88-dependent and MyD88-independent signaling in Porphyromonas gingivalis-elicited macrophage foam cell formation. Mol Oral Microbiol 28:28-39|
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