defects in the peripheral taste structure and function in the mrllpr mouse model of autoimmune disease在外围味觉结构和功能缺陷mrllpr自身免疫性疾病的小鼠模型.pdf

Defects in the Peripheral Taste Structure and Function in the MRL/lpr Mouse Model of Autoimmune Disease Agnes Kim.¤, Pu Feng., Tadahiro Ohkuri, Daniel Sauers, Zachary J. Cohn, Jinghua Chai, Theodore Nelson, Alexander A. Bachmanov, Liquan Huang, Hong Wang* Monell Chemical Senses Center, Philadelphia, Pennsylvania, United States of America Abstract While our understanding of the molecular and cellular aspects of taste reception and signaling continues to improve, the aberrations in these processes that lead to taste dysfunction remain largely unexplored. Abnormalities in taste can develop in a variety of diseases, including infections and autoimmune disorders. In this study, we used a mouse model of autoimmune disease to investigate the underlying mechanisms of taste disorders. MRL/MpJ-Faslpr/J (MRL/lpr) mice develop ¨ a systemic autoimmunity with phenotypic similarities to human systemic lupus erythematosus and Sjogren’s syndrome. Our results show that the taste tissues of MRL/lpr mice exhibit characteristics of inflammation, including infiltration of T lymphocytes and elevated levels of some inflammatory cytokines. Histological studies reveal that the taste buds of MRL/lpr mice are smaller than those of wild-type congenic control (MRL/+/+) mice. 5-Bromo-29-deoxyuridine (BrdU) pulse-chase experiments show that fewer BrdU-labeled cells enter the taste buds of MRL/lpr mice, suggesting an inhibition of taste cell renewal. Real-time RT-PCR analyses show that mRNA levels of several type II taste cell markers are lower in MRL/lpr mice. Immunohistochemical analyses confirm a significant reduction in the number of gustducin-positive taste receptor cells in the taste buds of MRL/lpr mice. F