Histopathological evaluation of multiple organs of 7-month-old HbSC mice. (A) Representative histological spleen sections stained with hematoxylin and eosin (H&E) of HbAA (right), HbSC (middle), and HbSS (left). Black arrows point to expanded red pulps with congested sinusoids, original magnification ×100. (B) Spleen-to-body-weight ratio. Scoring of splenic red pulp congestion (C) and atrophy of white pulps based on pathology scoring of the spleen (D; supplemental Table 1). (E) Representative H&E pictures of liver sections illustrating congestion (black arrows), and areas of infarcts (blue arrows), original magnification ×200. Insets showing Prussian blue staining for each group. (F) Liver-to-body-weight ratio. Scoring of hemosiderin (G), the liver congestion (H), and portal inflammation (I) based on pathology scoring of the liver (supplemental Table 2). Representative Masson trichrome staining of liver sections (original magnification ×400; J) and liver fibrosis scoring (K), see more details in (supplemental Table 2). (L) Representative H&E pictures of kidney sections with insets showing Prussian blue staining for each group (original magnification ×200). (M) Iron deposition in the renal tubes based on pathology scoring of the kidney (supplemental Table 3). (N) Representative Masson trichrome staining of kidney sections (original magnification ×400). (O) Urine osmolarity, 6 hours; mice were 6 months old in this test. (P) Representative H&E pictures of heart sections (original magnification ×400), with insets showing original magnification ×20. Statistics were performed using ANOVA. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .00001. (Q) Representative H&E-stained bone and femoral sections of 1-year-old HbAA (n = 3), HbSC (n = 3), and HbSS (n = 5) with normal bone architecture and hematopoietic marrow (R) with intact osteocytes occupying the lacunae. (S-U) One abnormal mouse from HbSS group. The SCD mouse exhibits features of bone pathology, including coagulative necrosis of the bone marrow and local bone infarction, characterized by empty osteocyte lacunae (highlighted inset). wt, weight.