Figure 4.
RelA heterozygosis prevents important progeroid features of Zmpste24−/− mice. (A) Reversal of skin alterations by NF-κB blockade. (Left panel) Ki-67 immunohistochemistry of 3-mo-old wild-type (n = 3), Zmpste24−/−RelA+/+ (n = 3), and Zmpste24−/−RelA+/− (n = 3) mice. Representative photographs are shown. Plot represents average number of Ki-67-positive cells ±SEM. P < 0.01, two-tailed Student's t-test. Bar, 30 μm. The right panel shows full recovery of the subcutaneous fat layer in 3-mo-old Zmpste24−/−RelA+/− mice as compared with Zmpste24−/−RelA+/+ littermates. Representative hematoxylin-eosin (H&E) staining micrographs are shown. Bar, 100 μm. (B) Thymus and spleen involution in Zmpste24-deficient mice is prevented in the RelA+/− background. (Top left panel) Representative photographs of spleen and thymus from 3-mo-old wild-type (n = 3), Zmpste24−/−RelA+/+ (n = 3), and Zmpste24−/−RelA+/− (n = 3) mice are shown. (Bottom left panel) Relative weight values of thymus and spleen are represented ±SEM. P < 0.01, two-tailed Student's t-test. The right panel shows representative micrographs from spleen and thymus tissues of wild-type, Zmpste24−/−RelA+/+, and Zmpste24−/−RelA+/− animals. Spleen details show representative lymphoid follicles; different regions are circled by dotted white lines (germinal center and mantle and marginal zones). Note that the Zmpste24−/−RelA+/+ thymus shows a notable tissue involution where lymphoid tissue has been mostly replaced by adipose tissue. Bar, 100 μm.