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Disturbed haem and globin synthesis in reticulocytes of prenatal flexed-tailed (f/f) anaemic mice

Published online by Cambridge University Press:  14 April 2009

R. J. Cole
Affiliation:
Genetics and Development Group, School of Biological Sciences, University of Sussex, Brighton
J. Garlick
Affiliation:
Genetics and Development Group, School of Biological Sciences, University of Sussex, Brighton
R. G. Tarbutt
Affiliation:
Genetics and Development Group, School of Biological Sciences, University of Sussex, Brighton
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Haem synthetase activity and co-ordination of α- and β-globin chain synthesis have been investigated in prenatal reticulocytes of congenic FL/4Re +/+ Lvb/Lvb and FL/1 Ref/f Lvb/Lvb, mice, which have a marked hypochromic, microcytic, siderocytic anaemia, with reduced erythrocyte numbers at birth, and also in other stocks bearing the f lesion. Haem synthetase activity in f/f reticulocyte homogenates was similar to that in normal cells but was markedly dependent on protoporphyrin added to the homogenate, while activity in normal cell homogenates was relatively independent of added precursor. In cultured normal prenatal reticulocytes α- and β-globin was synthesized in approximately equal amounts during a 4 h labelling period, but in f/f reticulocytes there was an approximate 50% deficiency in β-globin chain synthesis. This deficiency could be repaired by added haem but not by protoporphyrin. Such a lesion is quantitatively consistent with the observed hypochromia of neonatal f/f erythrocytes. The relationship of this abnormality to effects of the f locus on early erythropoietic precursor cells is discussed.

Type
Research Article
Copyright
Copyright © Cambridge University Press 1974

References

REFERENCES

Adamson, S. D., Herbert, E. & Kemp, S. F. (1969). Effects of hemin and other porphyrins on protein synthesis in a reticulocyte lysate cell free system. Journal of Molecular Biology 42, 247258.CrossRefGoogle Scholar
Bank, A., Braverman, A. S. & O'Donnell, J. V. (1968). Absolute rates of globin chain synthesis in thalassemia. Blood 31, 226233.CrossRefGoogle ScholarPubMed
Bateman, A. E. & Cole, R. J. (1972). Colony forming cells in the livers of prenatal flexed (f/f) anaemic mice. Cell and Tissue Kinetics 5, 165173.Google Scholar
Bateman, A. E., Cole, R. J., Regan, T. & Tarbutt, R. G. (1972). The role of erythropo-ietin in prenatal erythropoiesis of congenitally anaemic flexed-tailed (f/f) mice. British Journal of Haematology 22, 415427.CrossRefGoogle ScholarPubMed
Clegg, J. B., Naughton, M. A. & Weatherall, D. J. (1966). Abnormal human haemoglobins, separation and characterisation of the a and β chains by chromatography. Journal of Molecular Biology 19, 91108.CrossRefGoogle ScholarPubMed
Clegg, J. B. & Weatherall, D. J. (1967). Hemaglobin synthesis in a thalassemia (haemoglobin H disease). Nature 215, 12411243.CrossRefGoogle Scholar
Cole, R. J., Regan, T. & Tarbutt, R. G. (1972). Haemoglobin synthesis in reticulocytes of prenatal f/f anaemic mice. British Journal of Haematology 23, 443452.CrossRefGoogle ScholarPubMed
Coleman, D., Russell, E. S. & Levin, E. (1969). Enzymatic studies of the hemopoietic defect in flexed mice. Genetics 61, 631–42.CrossRefGoogle ScholarPubMed
Fantoni, A., Bank, A. & Marks, P. A. (1967). Globin composition and synthesis of hemoglobins in developing fetal mice erythroid cells. Science 157, 13271329.CrossRefGoogle ScholarPubMed
Fantoni, A., Chapelle, A., Rifkind, R. A. & Marks, P. A. (1968). Erythroid cell development in fetal mice: synthetic capacity for different proteins. Journal of Molecular Biology 33, 7995.CrossRefGoogle ScholarPubMed
Fowler, J. H., Till, J. E., McCulloch, E. A. & Siminovitch, L. (1967). The cellular basis for the defect in hemopoiesis in flexed-tailed mice. 2. The specificity of the defect for erythropoiesis. British Journal of Haematology 13, 250264.CrossRefGoogle ScholarPubMed
Fowler, J. H. & Russell, E. S. (1968). Fetal erythropoiesis in flexed mice. (Abstr.) Genetics 60, 178.Google Scholar
Freshney, R. I. & Paul, J. (1971). The activities of three haem-synthesizing enzymes during hepatic erythropoiesis in the mouse. Journal of Embryology and Experimental Morphology 26, 313322.Google Scholar
Hunt, T., Hunter, T. & Munro, A. (1969). Control of hemoglobin synthesis: rate of translation of the messenger RNA for the α and β chains. Journal of Molecular Biology 43, 123133.CrossRefGoogle ScholarPubMed
Hunt, T., Vanderhoff, G. & London, I. M. (1972). Control of globin synthesis; the role of heme. Journal of Molecular Biology 66, 471481.CrossRefGoogle ScholarPubMed
Jacobs-Lorena, M. & Baglioni, C. (1972). Messenger RNA for globin in the post-ribosomal supernatant of rabbit reticulocytes. Proceedings of the National Academy Science, U.S.A. 69, 14251428.CrossRefGoogle Scholar
Kappas, A. & Granick, S. (1968). Steroid induction of porphyrin synthesis in liver cell culture. Journal of Biological Chemistry 243, 346351.CrossRefGoogle ScholarPubMed
Lodish, H. F. & Jacobsen, M. (1972). Regulation of hemoglobin synthesis equal rates of translation and termination of α and β globin chains. Journal of Biological Chemistry 247, 36223629.CrossRefGoogle Scholar
Margolis, F. L. & Russell, E. S. (1965). Delta-aminolevulinate dehydratase activity in mice with hereditary anaemia. Science 150, 496497.CrossRefGoogle Scholar
Marks, P. A. & Bank, A. (1972). Molecular pathology of the thalassemia syndromes. Federation Proceedings 30, 977982.Google Scholar
Nathan, D. G., Lodish, H. F., Kan, Y. W. & Housman, D. (1971). Beta-thalassemia and translation of globin messenger RNA. Proceedings of the National Academy of Sciences, U.S.A. 68, 25142518.CrossRefGoogle ScholarPubMed
Paul, J., Conkie, D. & Freshney, R. I. (1969). Erythropoietic cell population changes during the hepatic phases of erythropoiesis in the foetal mouse. Cell & Tissue Kinetics 2, 283294.Google Scholar
Rabinovitz, M., Freedman, M., Fisher, J. M. & Maxwell, C. R. (1969). Translational control in haemoglobin synthesis. Cold Spring Harbor Symposium, Quantitative Biology 34, 567578.CrossRefGoogle Scholar
Schwartz, E. (1970). Heterozygous beta thalassemia: balanced globin synthesis in bone marrow cells. Science 167, 15131514.CrossRefGoogle ScholarPubMed
Tarbutt, R. G. & Cole, R. J. (1970). Cell population kinetics in the livers of foetal mice. Journal of Embryology & Experimental Morphology 24, 249, 429446.Google ScholarPubMed
Tarbutt, R. G. & Cole, R. J. (1972). Foetal erythropoiesis in congenitally anaemic flexed-tailed (f/f) mice. Cell and Tissue Kinetics 5, 491503.Google Scholar
Tavill, A. S., Grayzel, A., London, I. M., Williams, M. K. & Vanderhoff, G. (1968). The role of haem in the synthesis and assembly of hemoglobin. Journal of Biological Chemistry 243, 49874999.CrossRefGoogle ScholarPubMed
Thompson, M., McCullooh, E., Siminovitoh, L. & Till, J. (1966). The cellular basis for the defect in hemopoiesis in flexed-tailed mice. I. The nature and persistence of the defect. British Journal of Haematology 12, 152160.CrossRefGoogle ScholarPubMed
Waxman, H. S., Freedman, M. L. & Rabinovitz, M. (1967). Studies with 59Fe labelled hemin on the control of polyribosome formation in rabbit reticulocytes. Biochimica et Biophysica Acta 145, 353360.CrossRefGoogle ScholarPubMed
White, J. M., Brain, M. C. & Ali, M. A. (1971). Globin synthesis in sideroblastic anaemia. I. α and β peptide chain synthesis. British Journal of Haematology 20, 263275.CrossRefGoogle ScholarPubMed
Zucker, W. V. & Schulman, H. M. (1968). Stimulation of globin chain initiation by hemin in the reticulocyte cell free system. Proceedings of the National Academy of Science, U.S.A. 59, 582589.CrossRefGoogle ScholarPubMed