Establishment of an atopic dermatitis-like skin model in a hairless mouse by repeated elicitation of contact hypersensitivity that enables to conduct functional analyses of the stratum corneum with various non-invasive biophysical instruments.
OBJECTIVE
Pathogenesis of atopic dermatitis (AD) has been studied in animal models such as the NC/Nga mouse strain or Balb/C mice that are repeatedly treated with 2,4,6-trinitro-1-chrolobenzene (TNCB). These mice exhibit features of chronic contact dermatitis, including an intensified early type skin reaction, increased number of mast cells and elevated serum IgE levels with a shift of cutaneous cytokine expression from a type 1 to type 2 profile. However, it is difficult to investigate the unique skin changes of AD such as dry skin, barrier dysfunction, and increased turnover of the stratum corneum (SC) in these animals with biophysical instruments because of the presence of their fur coats. In this study, we succeeded in establishing a mouse model of AD in hairless mice that are suitable for various functional analyses of the SC as well as for examining the immunological characteristics of human AD by treating TNCB-contact sensitized hairless mice with 1% TNCB every other day for 36 days.


METHODS
In hairless animals treated with TNCB every 2 days for 36 days, we measured time courses of skin swelling induced by contact hypersensitivity reaction on days 0, 6, 20 and 36. During the time course, non-invasive measurements for skin surface condition with biophysical instruments were conducted, and the area size and the rear surface villi of corneocytes obtained were measured. Also skin samples and blood samples were taken at each time point for histology and measurement of serum IgE level.


RESULTS
A gradual intensification of an early type contact hypersensitivity reaction was observed over the treatment period. These mice exhibited reduced SC hydration, heightened trans-epidermal water loss, and increased skin thickness. These mice also showed a decrease in the surface area size of each corneocytes and marked villus formation on their rear surface. Histologically, there was an increase in the number of CD4 and CD8 positive T cells in the epidermis. Also observed was a marked increase in the number of dermal mast cells and eosinophils, which correlated with elevated serum IgE levels induced by TNCB treatments.


CONCLUSIONS
From the results obtained we conclude that repeated treatments of TNCB-sensitized hairless mice with TNCB provides a useful means by which to study the pathological characteristics of AD skin lesions as well as their immunological characteristics.
Matsumoto
Katsuo
K
POLA Laboratories, Yokohama, Japan. Katsuom@pola.co.jp
Mizukoshi
Koji
K
Oyobikawa
Midori
M
Ohshima
Hiroshi
H
Tagami
Hachiro
H
D000287:Administration, Topical; D000818:Animals; D001703:Biophysics / Q000295:instrumentation; D003876:Dermatitis, Atopic / Q000139:chemically induced* / Q000175:diagnosis / Q000473:pathology* / Q000503:physiopathology; D003877:Dermatitis, Contact / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004817:Epidermis / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D051379:Mice; D008812:Mice, Hairless; D010853:Picryl Chloride / Q000008:administration & dosage / Q000506:poisoning*; D012869:Skin Absorption; D013601:T-Lymphocytes / Q000187:drug effects / Q000473:pathology; D014870:Water Loss, Insensible / Q000187:drug effects
D007073:Immunoglobulin E; D010853:Picryl Chloride