Pathology of mice expressing exclusively HbS and human γ-chains
| . | NY1KO + γL . | NY1KO + γM . | NY1KO + γH . | BERK . | BERK + γM . |
|---|---|---|---|---|---|
| HbF/retics | >3% γ/63% retics | 20% γ/30% retics | 40% γ/13% retics | >1% γ/37% retics | 21% γ/37% retics |
| Spleen | Congestive splenomegaly 2/2 Fe 2/2 Slight fibrosis 2/2 | Congestive splenomegaly 3/3 Fe 2/3 Fibrosis 2/3 | Congestive splenomegaly 4/4 Fe 3/4 Focal necrosis 2/4 | Congestive splenomegaly 2/2 Fe 2/2 Fibrosis 2/2 | Congestive splenomegaly 2/2 Fe 2/2 Organizing infarct 1/2 |
| Liver | Hematopoiesis 2/2 Sinusoids packed 2/2 Mild necrosis 1/2 Central vein dilated 1/2 | Moderate hematopoiesis 3/3 Sinusoids packed 1/3 Necrosis/fibrosis 3/3 Central vein dilated 1/3 | Little hematopoiesis 4/4 Moderate congestion 2/4 Focal necrosis 3/4 Central vein dilated 1/4 Fe in Kupfer cells 1/4 | Moderate hematopoiesis 2/2 Severe congestion 2/2 Necrosis 2/2 | Hematopoiesis 2/2 Moderate congestion 2/2 Small areas of necrosis 1/2 Fe in Kupfer cells 2/2 |
| Kidney | Medullary congestion 2/2 Focal hypercellular glomeruli 2/2 Tubular atrophy 1/2 Proliferating epithelial cells 1/2 | Congestion 2/3 Distended glomeruli 2/3 Fe tubules/cortex 1/3 Scarring cortex 2/3 | Mild congestion 2/4 Atrophy 1/4 Focal scarring 2/4 Minimal fibrosis 2/4 Microcysts 1/4 | Medullary congestion 2/2 Congested glomeruli 2/2 Scarring cortex 2/2 | Mild congestion 2/2 Hypercellular glomeruli 2/2 Tubular degeneration 1/2 Fe 1/2 |
| Brain | Normal | Pycnotic Purkinje 2/3 Lacunae 1/3 Scarring 1/3 Autolytic area 1/3 | Normal | Purkinje intact 2/2 Some scarring 1/2 Packed vessels 1/2 | Congested 1/2 |
| Heart | Hypertrophy 1/2 Focal right ventricular interstitial fibrosis 1/2 | Right/left hypertrophy 2/3 Scarring 1/3 | Perivascular fibrosis 1/4 Left atrial thrombosis 1/4 | Right/left hypertrophy 2/2 Mild fibrosis 1/2 | Right ventricular hypertrophy 1/2 |
| Age (d) | 35, 51 Note very young age | 44, 65, 167 Oldest most severe | 87, 137, 148, 172 | 69, 169 | 83, 164 |
| . | NY1KO + γL . | NY1KO + γM . | NY1KO + γH . | BERK . | BERK + γM . |
|---|---|---|---|---|---|
| HbF/retics | >3% γ/63% retics | 20% γ/30% retics | 40% γ/13% retics | >1% γ/37% retics | 21% γ/37% retics |
| Spleen | Congestive splenomegaly 2/2 Fe 2/2 Slight fibrosis 2/2 | Congestive splenomegaly 3/3 Fe 2/3 Fibrosis 2/3 | Congestive splenomegaly 4/4 Fe 3/4 Focal necrosis 2/4 | Congestive splenomegaly 2/2 Fe 2/2 Fibrosis 2/2 | Congestive splenomegaly 2/2 Fe 2/2 Organizing infarct 1/2 |
| Liver | Hematopoiesis 2/2 Sinusoids packed 2/2 Mild necrosis 1/2 Central vein dilated 1/2 | Moderate hematopoiesis 3/3 Sinusoids packed 1/3 Necrosis/fibrosis 3/3 Central vein dilated 1/3 | Little hematopoiesis 4/4 Moderate congestion 2/4 Focal necrosis 3/4 Central vein dilated 1/4 Fe in Kupfer cells 1/4 | Moderate hematopoiesis 2/2 Severe congestion 2/2 Necrosis 2/2 | Hematopoiesis 2/2 Moderate congestion 2/2 Small areas of necrosis 1/2 Fe in Kupfer cells 2/2 |
| Kidney | Medullary congestion 2/2 Focal hypercellular glomeruli 2/2 Tubular atrophy 1/2 Proliferating epithelial cells 1/2 | Congestion 2/3 Distended glomeruli 2/3 Fe tubules/cortex 1/3 Scarring cortex 2/3 | Mild congestion 2/4 Atrophy 1/4 Focal scarring 2/4 Minimal fibrosis 2/4 Microcysts 1/4 | Medullary congestion 2/2 Congested glomeruli 2/2 Scarring cortex 2/2 | Mild congestion 2/2 Hypercellular glomeruli 2/2 Tubular degeneration 1/2 Fe 1/2 |
| Brain | Normal | Pycnotic Purkinje 2/3 Lacunae 1/3 Scarring 1/3 Autolytic area 1/3 | Normal | Purkinje intact 2/2 Some scarring 1/2 Packed vessels 1/2 | Congested 1/2 |
| Heart | Hypertrophy 1/2 Focal right ventricular interstitial fibrosis 1/2 | Right/left hypertrophy 2/3 Scarring 1/3 | Perivascular fibrosis 1/4 Left atrial thrombosis 1/4 | Right/left hypertrophy 2/2 Mild fibrosis 1/2 | Right ventricular hypertrophy 1/2 |
| Age (d) | 35, 51 Note very young age | 44, 65, 167 Oldest most severe | 87, 137, 148, 172 | 69, 169 | 83, 164 |