Title

Generation and characterization of the CD13/aminopeptidase N knockout mouse

Date of Completion

January 2009

Keywords

Biology, Cell

Degree

Ph.D.

Abstract

The major goal of our laboratory is to study the functions of membrane bound peptidase CD 13/Aminopeptidase N in normal physiology, as well as in disease states. CD13 is best known for its enzymatic activity dependent functions with the most important being metabolism of regulatory peptides in epithelial cells of the small intestine, proximal tubules of the kidney, and in the synaptic membranes of the brain. Many studies published in the literature associate CD13 enzymatic activity-dependent and independent functions with processes such as angiogenesis, phagocytosis, chemotaxis, signaling, cell adhesion, cytokine metabolism, and hematopoiesis. CD13 has been shown to be expressed on most cells of the immune system during lineage development, as well as in the mature states, although its function in those cells has not yet been defined. In addition to steady state expression, CD13 has been implicated in inflammatory diseases such as multiple sclerosis, asthma, arthritis, and inflammatory bowel disease. Given that CD13 appears to be widely expressed and has many functions ascribed to it in the literature, in order to better understand the role of this peptidase in vivo we have generated a CD13 knockout mouse. We have demonstrated that the animals appeared to be healthy and exhibited normal breeding behavior. The results generated from the in vitro and in vivo studies indicated that CD13 expression was dispensable to most of the functions and disease models tested except dendritic cell antigen cross-presentation. We have determined that CD13 might play a role in dendritic cell cross-presentation of soluble antigens in the context of MHC class I molecules resulting in augmented CD8 lymphocyte activation as compared to their WT counterparts. The extent of our experiments did not yield sufficient enough evidence to implicate CD13 in disease pathogenesis. Further studies are necessary to dissect physiologically relevant CD13 functions, if any, in the context of the immune system. ^