942 Tmem79 Deficient Mice Sequentially Develop Dermatitis Associated with S.aureus Non-Dominant and Dominant Dysbioses
The journal of investigative dermatology/Journal of investigative dermatology(2018)
Abstract
S.aureus-dominant dysbiosis has been reported to be associated with atopic dermatitis (AD). In this study, we investigated the association of dermatitis with dysbiosis caused by the deficiency of Tmem79, the responsible gene for AD-like dermatitis observed in flaky tail (ft) mice. We generated complete knockout mice of Tmem79 (Tmem79-/-) to eliminate the influence of truncated Tmem79 protein expressed in ft mice, and analyzed the time-dependent changes of dermatitis and skin microbiota. Skin severity score and scratching behavior analysis under SPF condition revealed that Tmem79-/- mice spontaneously developed dermatitis at 34 weeks old (first phase), followed by temporal improvement and subsequently more severe dermatitis after 12 weeks old (second phase). Skin microbiota composition analysis by 16S rRNA sequencing and quantification analysis of the total amount of 16S rRNA PCR amplicon which would reflect the total number of microbiota revealed no major compositional change with five-fold increment of the total amount of 16S rRNA PCR amplicon at the first phase of dermatitis, and S.aureus-dominant dysbiosis with gradual increment of the PCR amplicon amount at the second phase of dermatitis. Antibiotic-treatment with cephalexin and enrofloxacin cocktail improved both phases of dermatitis. Although this treatment reversed dermatitis with S.aureus-dominant dysbiosis in the second phase, it recurred after suspension of the antibiotic treatment. Taken together, Tmem79-/- mice sequentially developed dermatitis associated with S.aureus non-dominant and dominant dysbioses. Although the elucidation of molecular function of Tmem79 is still remaining, Tmem79-/- mice would potentially provide an important clue for clarification of mechanism of dermatitis with both S.aureus non-dominant and dominant dysbioses.
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