title: Noninvasive monitoring of diabetes-induced cutaneous nerve fiber loss and hypoalgesia in thy1-YFP transgenic mice.
abstract: Progressive loss of pain perception and cutaneous nerve fibers are frequently observed in diabetic patients. We evaluated the feasibility of using thy1-YFP mice that express the yellowish-green fluorescent protein (YFP) in all of their sensory/motor neurons for noninvasive monitoring of cutaneous nerve fiber loss during diabetes. Fluorescent fibers in skin sections from the leg of thy1-YFP mice stained positive for the neuron-specific protein gene product 9.5 (PGP9.5), indicating that the cutaneous fluorescent fibers are indeed nerve fibers. In diabetic thy1-YFP mice, significant small cutaneous nerve fiber loss in the leg was observed at 3 months following the onset of diabetes, but loss of heat-induced pain perception occurred as early as 1 month following the onset of diabetes, indicating that functional impairment of sensory nerves precedes cutaneous nerve fiber loss. Immunostaining of skin sections of mice killed at 6 months following the onset of diabetes showed that parallel to the loss of small fluorescent nerve fibers, there was a significant decrease in fibers stained positive for calcitonin gene-related peptide, substance P, and purinoreceptor subtype in diabetic thy1-YFP mice. These mice will be useful for noninvasive monitoring of cutaneous nerve fiber degeneration and loss of heat-induced pain perception during diabetes and for the assessment of efficacy of therapeutic treatment of diabetic neuropathy.
authors.affiliation: Department of Anatomy, The University of Hong Kong, Hong Kong, China.
authors.forename: Yuk Shan
authors.initials: YS
authors.lastname: Chen
authors.forename: Stephen S M
authors.initials: SS
authors.lastname: Chung
authors.forename: Sookja K
authors.initials: SK
authors.lastname: Chung
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000032:analysis* / Q000235:genetics; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000503:physiopathology*; D005786:Gene Expression Regulation; D017930:Genes, Reporter / Q000235:genetics; D008164:Luminescent Proteins / Q000032:analysis* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009412:Nerve Fibers / Q000473:pathology*; D010146:Pain / Q000503:physiopathology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012867:Skin / Q000294:innervation*; D018800:Thy-1 Antigens / Q000235:genetics*; D013997:Time Factors; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D001786:Blood Glucose; D008164:Luminescent Proteins; D018800:Thy-1 Antigens; C054562:yellow fluorescent protein, Bacteria; D043222:Ubiquitin Thiolesterase; C496976:Uchl1 protein, mouse