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Iron homeostasis in the brain: complete iron regulatory protein 2 deficiency without symptomatic neurodegeneration in the mouse

Nature Genetics volume 38, pages 967–969 (2006)Cite this article

To the Editor:

Abnormalities in brain iron metabolism cause or contribute to severe human neurological disorders1. It is therefore critical to unravel the mechanisms controlling brain iron metabolism, which are presently not well understood. Strikingly, aged adult mice with a targeted deletion of the iron regulatory protein-2 (Ireb2) gene have been reported to suffer from a neurodegenerative movement disorder characterized by ataxia, bradykinesia and tremor2, associated with iron deposits in white matter tracts and nuclei throughout the brain, suggesting that deficiency for a key regulator of cellular iron homeostasis, IREB2, causes neurodegeneration by altering brain iron metabolism. Molecularly, increased ferritin expression has been noted in several areas of white and gray matter, preceding axonal degeneration with, importantly, a loss of Purkinje cells2.

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Figure 1: IREB2-deficient mice show largely normal locomotion and similar histological and ultrastructural brain morphologies as wild-type mice.

References

  1. Hentze, M.W., Muckenthaler, M.U. & Andrews, N.C. Cell 117, 285–297 (2004).

    Article  CAS  Google Scholar 

  2. LaVaute, T. et al. Nat. Genet. 27, 209–214 (2001).

    Article  CAS  Google Scholar 

  3. Galy, B., Ferring, D. & Hentze, M.W. Genesis 43, 181–188 (2005).

    Article  CAS  Google Scholar 

  4. Smith, S.R. et al. Ann. NY Acad. Sci. 1012, 65–83 (2004).

    Article  CAS  Google Scholar 

  5. Ohl, F., Holsboer, F. & Landgraf, R. Behav. Res. Methods Instrum. Comput. 33, 392–397 (2001).

    Article  CAS  Google Scholar 

  6. Brunk, U.T. & Terman, A. Free Radic. Biol. Med. 33, 611–619 (2002).

    Article  CAS  Google Scholar 

  7. Wahlsten, D. et al. J. Neurobiol. 54, 283–311 (2003).

    Article  Google Scholar 

  8. Olson, E.N., Arnold, H.H., Rigby, P.W. & Wold, B.J. Cell 85, 1–4 (1996).

    Article  CAS  Google Scholar 

  9. Bothe, G.W., Bolivar, V.J., Vedder, M.J. & Geistfeld, J.G. Genes Brain Behav. 3, 149–157 (2004).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank M. Hrabé de Angelis and the German Mouse Clinic for their work and the staff of the EMBL animal house and C. Schneider for technical assistance. This work was supported in part by the Bundesministerium für Bildung und Forschung/Nationales Genomforschungsnetz and Eumorphia (grant no. EU QLG2-CT-2002-00930), and by funds from the Gottfried-Wilhelm-Leibniz-Prize to M.W.H.

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Authors and Affiliations

  1. European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, Heidelberg, 69117, Germany

    Bruno Galy, Dunja Ferring & Matthias W Hentze

  2. Institute of Developmental Genetics, GSF-National Research Center for Environment and Health, Ingolstädter Landstrasse 1, Neuherberg, 85764, Germany

    Sabine M Hölter & Wolfgang Wurst

  3. Institute of Experimental Genetics, GSF-National Research Center for Environment and Health, Ingolstädter Landstrasse 1, Neuherberg, 85764, Germany

    Thomas Klopstock & Lore Becker

  4. Department of Neurology, Ludwig-Maximilians-Universität, Marchioninistrasse 15, München, 81377, Germany

    Thomas Klopstock & Lore Becker

  5. Max-Planck-Institüt of Psychiatry, Kraepelinstrasse 2-10, München, 80804, Germany

    Wolfgang Wurst

  6. Abteilung Zelluläre und Molekulare Pathologie, Deutsches Krebsforschungszentrum Heidelberg, Im Neuenheimer Feld 280, Heidelberg, 69120, Germany

    Sylvia Kaden & Hermann-Josef Gröne

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  9. Matthias W Hentze
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Supplementary information

Supplementary Fig. 1

IREB2-deficient mice display altered ferritin and TFR1 expression in the brain. (PDF 119 kb)

Supplementary Fig. 2

Assessment of balance and motor coordination in wild-type versus IREB2-deficient mice using the accelerating rotarod. (PDF 67 kb)

Supplementary Table. 1

Total non-heme iron content in the brain of IREB2-deficient mice versus wild-type mice. (PDF 42 kb)

Supplementary Table. 2

Phenotyping of wild-type versus IREB2-deficient mice using the modified hole board test. (PDF 126 kb)

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Galy, B., Hölter, S., Klopstock, T. et al. Iron homeostasis in the brain: complete iron regulatory protein 2 deficiency without symptomatic neurodegeneration in the mouse. Nat Genet 38, 967–969 (2006). https://doi.org/10.1038/ng0906-967

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