Ulcerative Dermatitis in C57BL/6 Mice Lacking Stearoyl CoA Desaturase 1

作者: James Ntambi , Lisa Krugner-Higby , Matthew T Flowers , Ogi Okwumabua , Melissa Behr

DOI:

关键词: Ulcerative dermatitisPathogenesisArthritisInflammatory bowel diseasePathologyEndocrinologyBiologyInflammationDietary lipidLesionStearoyl-CoA desaturase-1Internal medicine

摘要: Ulcerative dermatitis (UD) is a chronic and common disease of laboratory mice that often leads to euthanasia affected animals due its debilitating nature. The affects with the C57BL/6 (B6) background, female have an increased propensity for disease, occurrence in iNOS–/– mice.11,13,32 In addition, incidence UD increases age, some seasonality has been ascribed although these reports are conflicting.1,11,13,31,32 UD diagnosed clinically by observation excoriations involving face, ears, or dorsal cervicothoracic skin accompanied pruritus negative ectoparasite exam. histologic description classically includes ulceration adherent serocellular crust adjacent epidermal hyperplasia marked inflammation neutrophils, lymphocytes, macrophages, mast cells.1,11 postulated multifaceted etiology, interactions between environmental (dietary vitamin E humidity11,13,32), immunologic (preferential production Th1 response B6 mice1,11), bacteriologic (overgrowth Staphylococcus xylosus)37 factors. The normal flora staphylococcal species, including S. xylosus.33,37 However, examinations various dermal species humans dogs revealed differences their adherence cells once become involved inflammatory process.4,18,19 Both cellular invasion associated pathogenesis gram-positive cocci.4,8,18,19 Documentation pathogenicity xylosus not extensive, but organism can be used induce lesions tails SJL/J mice.33 Like mice, diabetic foot ulcers human beings also difficult treat complex etiology. initial lesion ulcer may vascular, colonization infection spreading ulcerative bacteria part pathogenesis.5,36 Likewise, whatever initiating event UD, bacterial important maintenance spread lesions. Stearoyl Co-A desaturase 1 (SCD1) enzyme catalyzes rate-limiting step creation monounsaturated fatty acids. Mice lack SCD1 gene (SCD1–/– mice) decreased expression genes coding enzymes synthesize lipids encoding oxidize These insulin sensitivity, body adiposity, resistance diet-induced obesity.20,25 SCD1–/– changes skin, sparse pelage absence guard hairs, hypoplasia meibomian sebaceous glands, progressive scarring (nonulcerative) alopecia.21,28,38 Conjugated linoleic acid (CLA) naturally occurring lipid several potentially therapeutic effects.2,7,26 CLA had antiinflammatory effects mouse model bowel 2 models autoimmune disease.2,7,26 New Zealand white which as systemic lupus erythrematosis, were fed standard semipurified rodent diet (NIH AIN76A) plus 1% survived longer than did control DBA/1J collagen-induced arthritis same concentration less joint controls.7 Recently, shown enhance wound healing mice.26 During nutritional studies using when changed from chow AIN93).10 This initiated investigation determine whether similar was based on NIH AIN76A serve useful study UD.7 nutrients semi-purified diets derived individual single-source components, so lipid, protein, carbohydrate source varying single component. Semipurified conditions like coronary artery where dietary plays role lesion. this type study, atherogenic fish oils substituted more beef tallow sole diet.12,16 We hypothesized at least one components development addition base would inhibit process. We ability invade underlying affect invasion. To test our hypotheses, then switched diet, corn oil fat source. Microbial isolates groups examined cell assay different 3T3 murine fibroblast origin.

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