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DEVELOPMENT OF TRANSGENIC ZEBRAFISH MODEL FOR INVESTIGATION OF THE FUNCTION OF MICROGLIAZebrafish have emerged as a powerful model organism for elucidating the development and function of microglia. Generation of new transgenic reporter lines and imaging tools strengthen the zebrafish model in microglia study�in-vivo. The aim is to develop a novel compound transgenic line to study the inflammatory process mediated by NF-kB in microglia cells. This novel compound transgenic line will establish a new model for microglia study. To generate the novel compound zebrafish transgenic model for microglia, we are crossbreeding microglia transgenic line zebrafish (Tg(mpeg1:mCherry) with the NF-kB Tg(6xNFkB:EGFP) transgenic progeny. We first generate a heterozygous F1 progeny which will be bred to generate an F2 homozygous progeny. Once the F1 progeny of the Microglia-NfkB transgenic line is developed, they will be crossbred to develop the Homozygous compound transgenic line. Fluorescent Microscopy will be used to screen the larvae generated from the breeding events. By developing the compound transgenic line, we are optimizing microglia isolation and sorting methodology by using the related antibodies as the marker. The NF-kB microglia transgenic line will provide a unique platform for drug screening to address microglial based ailments, thus furthering the understanding and treatment of human disease.
Role of the Aryl Hydrocarbon Receptor (Ahr) in Skeletal MuscleThe AhR is a ligand-activated transcription factor known to mediate the negative effects of environmental contaminants such as dioxin. Inactivation of AhR in skeletal muscle appears to be a response to both resistance exercise training and endurance exercise training, whereas activation of the receptor impairs tissue regeneration in zebrafish. AhR is also a receptor for kynurenine, an oxidized metabolite of the aromatic amino acid tryptophan. We have found that while tryptophan can preserve lean mass and stimulate muscle-derived IGF-1 in the setting of dietary protein deficiency, kynurenine decreases both muscle mass and IGF-1. Aside from these few studies, very little is known about the role of AhR in muscle wasting in catabolic settings such as aging or disease, or how it mediates the response to exercise. We have identified expression of the AhR in skeletal muscle using immunostaining and gene expression (PCR) of mouse hindlimb muscles (tibialis anterior). We are currently working to determine whether AhR expression levels change with age, or differ between males and females. The ultimate goal of this research is to develop novel therapeutic approaches, perhaps targeting AhR, to prevent muscle loss with aging and disuse. Funding Source: National Institute on Aging