Abstract

HUMAN SKIN - NUDE MOUSE MODEL. We have established a model for long-term cultivation of adult human skin on the nude athymic mouse. Psoriatic skin can be grown for periods of several months and retain the essential features of psoriasis. Epidermal kinetics studies confirm a hyperproliferative state in these grafts. Recombinant studies of normal and psoriatic epidermis and dermis have localized the site of the pathologic defect in psoriasis to both epidermis and dermis. Studies are also underway utilizing the human skin-nude mouse system to study conservation of regional epidermal specificities and the effect of non-dermal connective tissue on epidermal maintenance. Epidermal kinetic studies are also underway on normal adult human skin to measure the percentage of cycling cells (growth fraction). Formation and Function of Structures at the Epidermal-Dermal Junction in Normal and Diseased Human Skin. Studies are underway to selectively isolate components of the epidermal-dermal junction, particularly anchoring fibrils. Crude """"""""anchoring fibril"""""""" enriched extracts have been obtained from human skin. A monoclonal antibody has been prepared that reacts with a normal human skin basement membrane antigen by immunofluorescent studies. On immunoelectronmicroscopy, monoclonal basement membrane zone antibody localized to the sub-basal lamina area, particularly associated with anchoring fibrils. Plans are to further document this association and to use this antibody as a tool to selectively isolate anchoring fibrils from crude """"""""anchoring fibril enriched"""""""" preparations.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR010546-24
Application #
3154708
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1977-05-01
Project End
1990-04-30
Budget Start
1989-05-01
Budget End
1990-04-30
Support Year
24
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599

  Publications

Jones, D A; Hunt 3rd, S W; Prisayanh, P S et al. (1995) Immunodominant autoepitopes of type VII collagen are short, paired peptide sequences within the fibronectin type III homology region of the noncollagenous (NC1) domain. J Invest Dermatol 104:231-5
Gammon, W R; Briggaman, R A (1993) Epidermolysis bullosa acquisita and bullous systemic lupus erythematosus. Diseases of autoimmunity to type VII collagen. Dermatol Clin 11:535-47
Gammon, W R; Briggaman, R A (1993) Bullous SLE: a phenotypically distinctive but immunologically heterogeneous bullous disorder. J Invest Dermatol 100:28S-34S
Gammon, W R; Murrell, D F; Jenison, M W et al. (1993) Autoantibodies to type VII collagen recognize epitopes in a fibronectin-like region of the noncollagenous (NC1) domain. J Invest Dermatol 100:618-22
Gammon, W R; Abernethy, M L; Padilla, K M et al. (1992) Noncollagenous (NC1) domain of collagen VII resembles multidomain adhesion proteins involved in tissue-specific organization of extracellular matrix. J Invest Dermatol 99:691-6
Gammon, W R; Fine, J D; Forbes, M et al. (1992) Immunofluorescence on split skin for the detection and differentiation of basement membrane zone autoantibodies. J Am Acad Dermatol 27:79-87
Woodley, D T; Yamauchi, M; Wynn, K C et al. (1991) Collagen telopeptides (cross-linking sites) play a role in collagen gel lattice contraction. J Invest Dermatol 97:580-5
Gammon, W R; Kowalewski, C; Chorzelski, T P et al. (1990) Direct immunofluorescence studies of sodium chloride-separated skin in the differential diagnosis of bullous pemphigoid and epidermolysis bullosa acquisita. J Am Acad Dermatol 22:664-70
Woodley, D T; Briggaman, R A; Herzog, S R et al. (1990) Characterization of ""neo-dermis"" formation beneath cultured human epidermal autografts transplanted on muscle fascia. J Invest Dermatol 95:20-6
Woodley, D T; Briggaman, R A; Gammon, W R (1990) Acquired epidermolysis bullosa. A bullous disease associated with autoimmunity to type VII (anchoring fibril) collagen. Dermatol Clin 8:717-26

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