A hypomorphic mouse model of dystrophic epidermolysis bullosa reveals mechanisms of disease and response to fibroblast therapy
J. Clin. Invest. Anja Fritsch, et al. 118:1669 doi:10.1172/JCI34292 [
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Figure 9Treatment of
Col7a1flNeo/flNeo mice with WT fibroblasts restores collagen VII deposition and function at the DEJZ.
(
A) In untreated skin of the hypomorph, collagen VII (green) was strongly reduced. (
B) Increased collagen VII levels were observed 7 days after 2 intradermal injections of 20 × 10
6 WT fibroblasts. (
C) The increased levels persisted for at least 21 days. Although clearly increased after the treatment, the collagen VII signals remained lower than in
Col7a1WT/WT controls (
D). Nuclei appear in red. (
E) Semiquantitative confocal microscopy (
n = 5 per group) using identical image settings demonstrated that the relative mean fluorescence intensity of collagen VII fluorescence signals at the DEJZ significantly increased 7 days after treatment of
Col7a1flNeo/flNeo animals with WT fibroblasts compared with untreated skin. *
P < 0.01, Student’s
t test. (
F) Collagen VII mRNA expression in the skin strongly increased 7 days after treatment of
Col7a1flNeo/flNeo animals with WT fibroblasts. Shown are RT-PCR products of
Col7a1 exons 1–3 from
Col7a1WT/WT skin (lane 1), untreated
Col7a1flNeo/flNeo skin (lane 2), and
Col7a1flNeo/flNeo skin 7 days after treatment (lane 3). GAPDH was used as a control. (
G) Microblisters at the DEJZ were induced by frictional stress in
Col7a1flNeo/flNeo animals. (
H) Treatment with intradermal injection of WT fibroblasts restored the resistance of the skin to shearing forces and abrogated blister formation in response to frictional stress. Scale bars: 25 μm.
