title: Defects in the peripheral taste structure and function in the MRL/lpr mouse model of autoimmune disease.
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-Fas(lpr)/J (MRL/lpr) mice develop a systemic autoimmunity with phenotypic similarities to human systemic lupus erythematosus and Sjögren'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-2'-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. Furthermore, MRL/lpr mice exhibit reduced gustatory nerve responses to the bitter compound quinine and the sweet compound saccharin and reduced behavioral responses to bitter, sweet, and umami taste substances compared with controls. In contrast, their responses to salty and sour compounds are comparable to those of control mice in both nerve recording and behavioral experiments. Together, our results suggest that type II taste receptor cells, which are essential for bitter, sweet, and umami taste reception and signaling, are selectively affected in MRL/lpr mice, a model for autoimmune disease with chronic inflammation.
authors.affiliation: Monell Chemical Senses Center, Philadelphia, Pennsylvania, United States of America.
authors.forename: Agnes
authors.initials: A
authors.lastname: Kim
authors.forename: Pu
authors.initials: P
authors.lastname: Feng
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Ohkuri
authors.forename: Daniel
authors.initials: D
authors.lastname: Sauers
authors.forename: Zachary J
authors.initials: ZJ
authors.lastname: Cohn
authors.forename: Jinghua
authors.initials: J
authors.lastname: Chai
authors.forename: Theodore
authors.initials: T
authors.lastname: Nelson
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Bachmanov
authors.forename: Liquan
authors.initials: L
authors.lastname: Huang
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002814:Chorda Tympani Nerve / Q000502:physiology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004848:Epithelium / Q000473:pathology; D005260:Female; D005930:Glossopharyngeal Nerve / Q000502:physiology; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011803:Quinine / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism; D012439:Saccharin / Q000494:pharmacology; D013601:T-Lymphocytes / Q000473:pathology; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism; D013650:Taste Buds / Q000378:metabolism / Q000473:pathology; D013651:Taste Disorders / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D014059:Tongue / Q000473:pathology; D014158:Transcription, Genetic; D015293:Transducin / Q000235:genetics / Q000378:metabolism; D000098706:Taste Receptors, Type 2
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D016207:Cytokines; D018836:Inflammation Mediators; D009419:Nerve Tissue Proteins; D011803:Quinine; D043562:Receptors, G-Protein-Coupled; D012439:Saccharin; D050053:TRPM Cation Channels; D015293:Transducin; D000098706:Taste Receptors, Type 2; C498617:Trpm5 protein, mouse; C075192:gustducin; C093564:Neurogenic differentiation factor 1