Hypothyroid mice and TR-deficient mice present similarly reduced proliferation in response to 9-cis-RA.

<p>Epidermal thickness (left panel) and BrdU incorporation (right panel) were determined in TR KO mice, mice treated with MMI and perchlorate for 4 months (hT) and in a group of animals receiving the anti-thyroidal drugs plus thyroxine (hT+T4).</p

TR deletion alters expression of loricrin.

<p>A) Localization by immunofluorescence of the terminal differentiation marker loricrin in the most external epidermal layer of skins from wild-type and TR KO mice treated with 9-cis-RA and TPA. Loricrin expression (red) demonstrates that 9-cis-RA (but not TPA) promotes altered differentiation and that this is more marked in mice lacking TRs. Panel B) shows that loricrin is totally absent in large areas of the skin of some TR KO animals after 9-cis-RA treatment.</p

Altered expression of proliferation-related proteins in the skin of TR-deficient mice after 9-cis-RA treatment.

<p>Total and nuclear skin cell lysates from Wt and KO mice treated topically with 9-cis-RA were used for Western blotting with the indicated antibodies. Actin and lamin B were used as a loading control for total and nuclear extracts, respectively.</p

Increased expression of proinflammatory and chemotactic molecules in skins of TR KO mice.

<p>Relative mRNA levels of TNFα, IL-6, S100A8 and S100A9 in wild-type and TR KO mice treated with vehicle, 9-cis-RA or TPA. Values representing expression levels of vehicle-treated wil-type mice were set to 1, and fold induction is represented relative to this basal level.</p

Expression of the proliferation marker keratin 5 is reduced in TR KO mice in response to proliferative stimuli.

<p>Examples of double immunofluorescence images of keratin 5 (K5, red) and β-catenin (green) expression in dorsal skin of wild-type (Wt) and TR-deficient mice (KO) after topical treatment with vehicle, 9-cis-RA or TPA. The slides were counterstained with dapi (blue) and the merged images are shown.</p

Immune cell infiltration is enhanced in skins of TR deficient mice treated with 9-cis-RA.

<p>Double immunofluorescence images of keratin 5 (K5) with mac-1 (left panel), cd45 (middle panel) and cd3ε (right panel) in skins from wild-type and TR KO mice treated with 9-cis-RA or vehicle alone. Nuclei were stained with dapi.</p

Keratin 6 and 10 expression in TR-deficient mice.

<p>A) The proliferation marker keratin 6 (K6, red) and the early differentiation marker keratin 10 (K10, green) were detected by immunofluorescence in wild-type and TR KO mice before and after application of 9-cis-RA or TPA. Nuclei were stained with dapi (blue). Panel B) represents a larger magnification of the merged images shown in A) for a better observation of K6 and K10 colocalization and the decrease in K10 expression observed in TR-deficient mice after 9-cis-RA treatment.</p

Reduced hyperplasia in response to retinoids in mice lacking TRs.

<p>Epidermal thickness was measured in wild-type and TR-deficient mice after topical treatment with all-trans-RA (ATRA) and 9-cis-RA. Data are shown as mean values ± SE, and ***(<i>P</i><0.001) represents statistically significant differences relative to Wt mice.</p