Hematology, globin mRNA amounts, globin chain synthesis, and red cell membrane proteins, at various time points in treated β-thalassemic mice
. | Wk . | Treated mice . | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
M1 . | M2 . | M3 . | M4 . | M5 . | M6 . | M7 . | M8 . | M9 . | ||
Serum Epo concentration (mU/mL) | −1 | 44.7 | 21.4 | 25.4 | 60.8 | 33.6 | 23.5 | 21.2 | 18.1 | 54.6 |
4 | 244.8 | 309.4 | 325.4 | 193 | 163 | 167 | 138.5 | 132.6 | 164 | |
11 | — | 295.6 | 194.1 | 157.8 | 80.7 | 117 | 138 | 142.7 | 145.5 | |
Hematocrit (%) | −1 | 33.1 | 33.3 | 32.5 | 32.4 | 34.2 | 33.3 | 32.4 | 30.7 | 34.1 |
4 | 80.5 | 70.3 | 55.6 | 53.5 | 49.6 | 46.7 | 45.3 | 39.8 | 38.2 | |
11 | — | 63.8 | 46.6 | 41 | 37.5 | 38.1 | 34.2 | 34.1 | 33.3 | |
Hemoglobin (g/dL) | −1 | 9.2 | 9 | 8.7 | 9.1 | 9.6 | 8.5 | 8.9 | 8.4 | 9.8 |
4 | 26.8 | 21.4 | 16 | 16.2 | 14.3 | 12.5 | 12.1 | 10.7 | 11.2 | |
11 | — | 18.6 | 13.1 | 11.6 | 10.4 | 9.9 | 8.9 | 9.2 | 9.7 | |
Red blood cell count (109cells/mL) | −1 | 9.8 | 9.2 | 9.6 | 8.9 | 9.4 | 9.5 | 9.7 | 8.8 | 9.9 |
4 | 19.5 | 17.4 | 13.3 | 13.6 | 13.3 | 12.2 | 13.7 | 10.7 | 10.6 | |
11 | — | 16.3 | 12.2 | 11 | 10.2 | 9.2 | 10.4 | 9.3 | 9.8 | |
Reticulocytes (%) | −1 | 28 | 31.1 | 27.3 | 27 | 30.7 | 30.3 | 29.2 | 32.2 | 26.8 |
4 | 9.6 | 13.3 | 14.8 | 15 | 20.5 | 19.6 | 21.5 | 26 | 22.6 | |
11 | — | 13.4 | 18.1 | 19.2 | 28.3 | 25.5 | 26.3 | 29 | 24 | |
βminor mRNA copy number | −1 | — | 18.3 | 18.1 | 18.1 | 17.3 | 15.3 | 15.3 | 16.3 | 14.4 |
4 | — | 48.3 | 44.7 | 35 | 32.1 | 26.9 | 28.7 | 17.5 | 15.7 | |
11 | — | 51.2 | 33.5 | 25.6 | 18.7 | 16.2 | 22.4 | 16.4 | 14.8 | |
α-globin mRNA copy number | −1 | — | 57.8 | 58 | 58 | 55.4 | 48.6 | 48.4 | 54.3 | 44.6 |
4 | — | 57.5 | 58.3 | 58.5 | 55 | 48.5 | 48.6 | 54.5 | 45 | |
11 | — | 57.7 | 58.1 | 58.2 | 55.6 | 48.9 | 48.5 | 54 | 44.2 | |
βminor/α-globin chain synthesis ratio | −1 | 0.72 | 0.71 | 0.68 | 0.74 | 0.69 | 0.64 | 0.68 | 0.63 | 0.71 |
4 | 0.98 | 0.96 | 0.90 | 0.88 | 0.81 | 0.80 | 0.75 | 0.65 | 0.76 | |
11 | — | 0.95 | 0.87 | 0.82 | 0.72 | 0.76 | 0.73 | 0.68 | 0.74 | |
α-chain content in erythrocyte membrane (% of −/−) | −1 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 |
4 | 1 | 37.9 | 70.5 | 69.8 | 77.5 | 79.2 | 45.5 | 92 | 98 | |
11 | — | 14.8 | 38.3 | 68.2 | 86.9 | 69.1 | 98.4 | 94.1 | 90.2 | |
Spectrin/band 3-globin ratio | −1 | 0.59 | 0.69 | 0.62 | 0.63 | 0.71 | 0.72 | 0.64 | 0.59 | 0.55 |
4 | 1.35 | 1.36 | 1.26 | 1.25 | 1.02 | 1 | 1.11 | 1.08 | 0.98 | |
11 | — | 1.37 | 1.31 | 1.22 | 1 | 1.2 | 0.86 | 0.83 | 0.76 | |
Band 3-globin area (% of total proteins) | −1 | 32.5 | 25.5 | 26 | 26.8 | 25.8 | 23.7 | 29.8 | 30.6 | 33.9 |
4 | 20 | 16.1 | 17.8 | 19.3 | 20.7 | 21.7 | 24.9 | 23 | 25.5 | |
11 | — | 15.5 | 17 | 20 | 21.1 | 20.1 | 27.1 | 28.2 | 27.3 | |
Spectrin α + β chains (% of total proteins) | −1 | 19.3 | 17.6 | 16.1 | 16.9 | 18.3 | 17.1 | 19.1 | 18 | 18.6 |
4 | 27 | 21.9 | 22.5 | 24.1 | 21.1 | 21.7 | 26.7 | 24.9 | 24.9 | |
11 | — | 21.2 | 22.4 | 24.5 | 21.1 | 24.2 | 23.3 | 23.3 | 20.8 | |
Membrane-bound Ig (% positive cells) | −1 | 12 | 11 | 11 | 11 | 10 | 9 | 10 | 12 | 13 |
4 | 2 | 3 | 6 | 5 | 6 | 4 | 7 | 8 | 10 | |
11 | — | 2 | 5 | 6 | 7 | 4 | 8 | 10 | 11 |
. | Wk . | Treated mice . | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
M1 . | M2 . | M3 . | M4 . | M5 . | M6 . | M7 . | M8 . | M9 . | ||
Serum Epo concentration (mU/mL) | −1 | 44.7 | 21.4 | 25.4 | 60.8 | 33.6 | 23.5 | 21.2 | 18.1 | 54.6 |
4 | 244.8 | 309.4 | 325.4 | 193 | 163 | 167 | 138.5 | 132.6 | 164 | |
11 | — | 295.6 | 194.1 | 157.8 | 80.7 | 117 | 138 | 142.7 | 145.5 | |
Hematocrit (%) | −1 | 33.1 | 33.3 | 32.5 | 32.4 | 34.2 | 33.3 | 32.4 | 30.7 | 34.1 |
4 | 80.5 | 70.3 | 55.6 | 53.5 | 49.6 | 46.7 | 45.3 | 39.8 | 38.2 | |
11 | — | 63.8 | 46.6 | 41 | 37.5 | 38.1 | 34.2 | 34.1 | 33.3 | |
Hemoglobin (g/dL) | −1 | 9.2 | 9 | 8.7 | 9.1 | 9.6 | 8.5 | 8.9 | 8.4 | 9.8 |
4 | 26.8 | 21.4 | 16 | 16.2 | 14.3 | 12.5 | 12.1 | 10.7 | 11.2 | |
11 | — | 18.6 | 13.1 | 11.6 | 10.4 | 9.9 | 8.9 | 9.2 | 9.7 | |
Red blood cell count (109cells/mL) | −1 | 9.8 | 9.2 | 9.6 | 8.9 | 9.4 | 9.5 | 9.7 | 8.8 | 9.9 |
4 | 19.5 | 17.4 | 13.3 | 13.6 | 13.3 | 12.2 | 13.7 | 10.7 | 10.6 | |
11 | — | 16.3 | 12.2 | 11 | 10.2 | 9.2 | 10.4 | 9.3 | 9.8 | |
Reticulocytes (%) | −1 | 28 | 31.1 | 27.3 | 27 | 30.7 | 30.3 | 29.2 | 32.2 | 26.8 |
4 | 9.6 | 13.3 | 14.8 | 15 | 20.5 | 19.6 | 21.5 | 26 | 22.6 | |
11 | — | 13.4 | 18.1 | 19.2 | 28.3 | 25.5 | 26.3 | 29 | 24 | |
βminor mRNA copy number | −1 | — | 18.3 | 18.1 | 18.1 | 17.3 | 15.3 | 15.3 | 16.3 | 14.4 |
4 | — | 48.3 | 44.7 | 35 | 32.1 | 26.9 | 28.7 | 17.5 | 15.7 | |
11 | — | 51.2 | 33.5 | 25.6 | 18.7 | 16.2 | 22.4 | 16.4 | 14.8 | |
α-globin mRNA copy number | −1 | — | 57.8 | 58 | 58 | 55.4 | 48.6 | 48.4 | 54.3 | 44.6 |
4 | — | 57.5 | 58.3 | 58.5 | 55 | 48.5 | 48.6 | 54.5 | 45 | |
11 | — | 57.7 | 58.1 | 58.2 | 55.6 | 48.9 | 48.5 | 54 | 44.2 | |
βminor/α-globin chain synthesis ratio | −1 | 0.72 | 0.71 | 0.68 | 0.74 | 0.69 | 0.64 | 0.68 | 0.63 | 0.71 |
4 | 0.98 | 0.96 | 0.90 | 0.88 | 0.81 | 0.80 | 0.75 | 0.65 | 0.76 | |
11 | — | 0.95 | 0.87 | 0.82 | 0.72 | 0.76 | 0.73 | 0.68 | 0.74 | |
α-chain content in erythrocyte membrane (% of −/−) | −1 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 |
4 | 1 | 37.9 | 70.5 | 69.8 | 77.5 | 79.2 | 45.5 | 92 | 98 | |
11 | — | 14.8 | 38.3 | 68.2 | 86.9 | 69.1 | 98.4 | 94.1 | 90.2 | |
Spectrin/band 3-globin ratio | −1 | 0.59 | 0.69 | 0.62 | 0.63 | 0.71 | 0.72 | 0.64 | 0.59 | 0.55 |
4 | 1.35 | 1.36 | 1.26 | 1.25 | 1.02 | 1 | 1.11 | 1.08 | 0.98 | |
11 | — | 1.37 | 1.31 | 1.22 | 1 | 1.2 | 0.86 | 0.83 | 0.76 | |
Band 3-globin area (% of total proteins) | −1 | 32.5 | 25.5 | 26 | 26.8 | 25.8 | 23.7 | 29.8 | 30.6 | 33.9 |
4 | 20 | 16.1 | 17.8 | 19.3 | 20.7 | 21.7 | 24.9 | 23 | 25.5 | |
11 | — | 15.5 | 17 | 20 | 21.1 | 20.1 | 27.1 | 28.2 | 27.3 | |
Spectrin α + β chains (% of total proteins) | −1 | 19.3 | 17.6 | 16.1 | 16.9 | 18.3 | 17.1 | 19.1 | 18 | 18.6 |
4 | 27 | 21.9 | 22.5 | 24.1 | 21.1 | 21.7 | 26.7 | 24.9 | 24.9 | |
11 | — | 21.2 | 22.4 | 24.5 | 21.1 | 24.2 | 23.3 | 23.3 | 20.8 | |
Membrane-bound Ig (% positive cells) | −1 | 12 | 11 | 11 | 11 | 10 | 9 | 10 | 12 | 13 |
4 | 2 | 3 | 6 | 5 | 6 | 4 | 7 | 8 | 10 | |
11 | — | 2 | 5 | 6 | 7 | 4 | 8 | 10 | 11 |
Epo indicates erythropoietin; Hb, hemoglobin; Ig, immunoglobulin.