Recently a transglutaminase 3 knockout (TGM3/KO) mouse was generated that showed impaired
hair development, but no gross defects in the epidermal barrier, although increased
fragility of isolated corneocytes was demonstrated. Here we investigated the functionality
of skin barrier in vivo by percutaneous sensitization to fluorescein-isothiocyanate
(FITC) in TGM3/KO (n=64) and C57BL/6 WT mice (n=36). Cutaneous inflammation was evaluated
by mouse ear swelling test (MEST), histology, serum IgE levels, and by flow-cytometry
from draining lymph nodes. Inflammation induced significant MEST difference (P<0.0001)
was detected between KO and WT mice and was supported also by histopathology. A significant
increase of CD4+ CD25+ activated T-cells (P<0.01) and elevated serum IgE levels (P<0.05)
in KO mice indicated more the development of FITC sensibilization than an irritative
reaction. P. acnes induced intracutaneous inflammation showed no difference (P=0.2254)
between the reactivity of WT and KO immune system. As in vivo tracer, FITC penetration
from skin surface followed by two-photon microscopy demonstrated a more invasive percutaneous
penetration in KO mice. The clinically uninvolved skin in TGM3/KO mice showed impaired
barrier function and higher susceptibility to FITC sensitization indicating that TGM3
has a significant contribution to the functionally intact cutaneous barrier.Journal
of Investigative Dermatology accepted article preview online, 24 July 2013. doi:10.1038/jid.2013.307.
