Erythropoiesis pp 103-115 | Cite as

Approaches for Analysis of Erythroid Cell Parameters and Hemoglobinopathies in Mouse Models

  • Marie Trudel
  • Josepha-Clara Sedzro
Part of the Methods in Molecular Biology book series (MIMB, volume 1698)


Over the last decades several mouse models of human hemoglobin disorders have been and continue to be generated. This chapter aims at describing various approaches to evaluate the global red blood cell properties in mouse models of human hemoglobin disorders, in particular thalassemia and sickle cell disease. Analysis of erythroid parameters provides insights into the RBC physiologic or pathophysiologic status. Mice expressing both murine and human globin genes can be investigated using adapted protocols provided herein.

Key words

Hemoglobin Globin chain Urea-triton polyacrylamide gel electrophoresis Cellulose acetate electrophoresis Smear 



This work was supported by Canadian Blood Services and Canadian Institute for Health Research grants to M.T.


  1. 1.
    Beauchemin H, Blouin MJ, Trudel M (2004) Differential regulatory and compensatory responses in hematopoiesis/erythropoiesis in a- and b-globin hemizygous mice. J Biol Chem 279(19):19471–19480CrossRefPubMedGoogle Scholar
  2. 2.
    Blouin M-J, Beauchemin H, Wright A, DePaepe M, Sorette M, Bleau A-M, Nakamoto B, Ou C-N, Stamatoyannopoulos G, Trudel M (2000) Genetic correction of sickle cell disease: insights using transgenic mouse models. Nat Med 6:177–182CrossRefPubMedGoogle Scholar
  3. 3.
    Felfly H, Trudel M (2010) Successful correction of murine sickle cell disease with reduced stem cell requirements reinforced by fractionated marrow infusions. Br J Haematol 148(4):646–658CrossRefPubMedGoogle Scholar
  4. 4.
    Pang CJ, Lemsaddek W, Alhashem YN, Bondzi C, Redmond LC, Ah-Son N, Dumur CI, Archer KJ, Haar JL, Lloyd JA, Trudel M (2012) Kruppel-like factor 1 (KLF1), KLF2, and Myc control a regulatory network essential for embryonic erythropoiesis. Mol Cell Biol 32(13):2628–2644. doi: 10.1128/mcb.00104-12 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Trudel M, Saadane N, Garel M-C, Bardakdjian-Michau J, Blouquit Y, Guerquin-Kern J-L, Rouyer-Fessard P, Vidaud D, Pachnis A, Romeo P-H, Beuzard Y, Costantini F (1991) Towards a transgenic mouse model of sickle cell disease: hemoglobin SAD. EMBO J 10(11):3157–3165PubMedPubMedCentralGoogle Scholar
  6. 6.
    Whitney JB III (1978) Simplified typing of mouse hemoglobin (Hbb) phenotypes using cystamine. Biochem Genet 16(7–8):667–672CrossRefPubMedGoogle Scholar
  7. 7.
    Stoyanova E, Trudel M, Felfly H, Garcia D, Cloutier G (2007) Characterization of circulatory disorders in b-thalassemic mice by noninvasive ultrasound biomicroscopy. Physiol Genomics 29:84–90CrossRefPubMedGoogle Scholar
  8. 8.
    Alter BP, Goff SC, Efremov GD, Gravely ME, Huisman THJ (1980) Globin chain electrophoresis: a new approach to the determination of the GgGg ratio in fetal haemoglobin and to studies of globin synthesis. Br J Haematol 44:527–534CrossRefPubMedGoogle Scholar
  9. 9.
    Beauchemin H, Trudel M (2009) Evidence for bigenic chromatin subdomain in fetal to adult hemoglobin switch regulation. Mol Cell Biol 29(6):1635–1648CrossRefPubMedGoogle Scholar
  10. 10.
    Rovera G, Magarian C, Borun TW (1978) Resolution of hemoglobin subunits by electrophoresis in acid urea polyacrylamide gels containing Triton X-100. Anal Biochem 85(2):506–518CrossRefPubMedGoogle Scholar
  11. 11.
    Ryan TM, Ciavatta DJ, Townes TM (1997) Knockout-transgenic mouse model of sickle cell disease. Science 278:873–876CrossRefPubMedGoogle Scholar
  12. 12.
    Paszty C, Brion CM, Manci E, Witkowska HE, Stevens ME, Mohandas N, Rubin EM (1997) Transgenic knockout mice with exclusively human sickle hemoglobin and sickle cell disease. Science 278:876–878CrossRefPubMedGoogle Scholar
  13. 13.
    Fabry ME, Bouhassira EE, Suzuka SM, Nagel RL (2003) Transgenic mice and hemoglobinopathies. Methods Mol Med 82:213–241. doi: 10.1385/1-59259-373-9:213 PubMedGoogle Scholar
  14. 14.
    Manci EA, Hillery CA, Bodian CA, Zhang ZG, Lutty GA, Coller BS (2006) Pathology of Berkeley sickle cell mice: similarities and differences with human sickle cell disease. Blood 107(4):1651–1658. doi: 10.1182/blood-2005-07-2839 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Trudel M, De Paepe ME, Chretien N, Saadane N, Jacmain J, Sorette M, Hoang T, Beuzard Y (1994) Sickle cell disease of transgenic SAD mice. Blood 84(9):3189–3197PubMedGoogle Scholar
  16. 16.
    De Paepe ME, Trudel M (1994) The transgenic SAD mouse: a model of human sickle cell glomerulopathy. Kidney Int 46(5):1337–1345CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2018

Authors and Affiliations

  1. 1.Molecular Genetics and Development, Institut de Recherches Cliniques de Montréal, Faculté de MédecineUniversité de MontréalMontrealCanada

Personalised recommendations