The Animal Core serves as a centralized resource that provides mice with genetic deletions or mutations to the members of the Center, other research groups at the university, and the general scientific community. The animal lines that we have focused on thus far have deletions of genes in three systems: opioid receptors (mu-, delta- and kappa-receptor subtypes), cannabinoid receptors (CB1, CB2 and CB1/2 double knockouts), and chemokine receptors and ligands (CCL2, CCR2 and CCR5). Significant progress to date has been made by multiple laboratories associated with the Center using these lines. In addition to continuing to breed the existing animal lines, in the next grant period we will breed combinatorial mutant mice with genetic deletions of multiple genes such as two opioid receptors (Le. mu/delta) or an opioid receptor together with a chemokine (Le. mu/CXCR2). In addition, we will include two new models: mice with conditional gene deletions using the Cre-LoxP system and mice that express specific proteins tagged with enhanced Green Fluorescent Protein (EGFP). Conditional gene deletions allow investigators to evaluate the function of specific proteins of interest within a specific cell type or brain region or within a specific time window without the embryonic lethality and/or developmental compensatory responses that limit the utility of constitutive knockout strategies. The first of these mice that the Animal Core will breed will be a CXCR4-floxed mouse line. EGFP-tagged mice allow researchers to monitor the expression and localization of the tagged protein of interest in vivo or in vitro without impacting protein function and without reliance on antibodies. The first two strains of EGFP transgenic mice that we propose to breed are the CXCR4- and CX3CR1-EGFP lines. Multiple proposals for the use of the existing and new animal lines are detailed in the application. In-house breeding and use of the same animal strains by multiple investigators enhances collaborative studies and increases scientific synergy. Furthermore, because some of our existing and proposed mouse strains are unavailable commercially, the Animal Core can serve as a national resource, providing unique mouse models to the scientific community.
The Animal Core is a resource that makes mice with gene deletions or mutations available to the scientific community. Mice with gene deletions or mutations are valuable animal models that allow researchers to examine the function of specific proteins in the brain. These animal models also provide important information about the pathophysiology of human disease.
|Console-Bram, Linda; Brailoiu, Eugen; Brailoiu, Gabriela Cristina et al. (2014) Activation of GPR18 by cannabinoid compounds: a tale of biased agonism. Br J Pharmacol 171:3908-17|
|Miller, Jonathan S; Barr, Jeffrey L; Harper, Lauren J et al. (2014) The GSK3 signaling pathway is activated by cocaine and is critical for cocaine conditioned reward in mice. PLoS One 9:e88026|
|Zhao, Pingwei; Lane, Tom R; Gao, Helen G L et al. (2014) Crucial positively charged residues for ligand activation of the GPR35 receptor. J Biol Chem 289:3625-38|
|Chatila, W M; Criner, G J; Hancock, W W et al. (2014) Blunted expression of miR-199a-5p in regulatory T cells of patients with chronic obstructive pulmonary disease compared to unaffected smokers. Clin Exp Immunol 177:341-52|
|Enman, Nicole M; Zhang, Yong; Unterwald, Ellen M (2014) Connecting the pathology of posttraumatic stress and substance use disorders: monoamines and neuropeptides. Pharmacol Biochem Behav 117:61-9|
|Shi, Xiangdang; Miller, Jonathan S; Harper, Lauren J et al. (2014) Reactivation of cocaine reward memory engages the Akt/GSK3/mTOR signaling pathway and can be disrupted by GSK3 inhibition. Psychopharmacology (Berl) 231:3109-18|
|Kong, Weimin; Li, Hongbo; Tuma, Ronald F et al. (2014) Selective CB2 receptor activation ameliorates EAE by reducing Th17 differentiation and immune cell accumulation in the CNS. Cell Immunol 287:1-17|
|Dimattio, K M; Yakovleva, T V; Aldrich, J V et al. (2014) Zyklophin, a short-acting kappa opioid antagonist, induces scratching in mice. Neurosci Lett 563:155-9|
|Lucchesi, Valentina; Hurst, Dow P; Shore, Derek M et al. (2014) CB2-selective cannabinoid receptor ligands: synthesis, pharmacological evaluation, and molecular modeling investigation of 1,8-Naphthyridin-2(1H)-one-3-carboxamides. J Med Chem 57:8777-91|
|Cathel, Alessandra M; Reyes, Beverly A S; Wang, Qin et al. (2014) Cannabinoid modulation of alpha2 adrenergic receptor function in rodent medial prefrontal cortex. Eur J Neurosci 40:3202-14|
Showing the most recent 10 out of 195 publications