Skip to main content
SpringerLink
Log in

OPA1, associated with autosomal dominant optic atrophy, is widely expressed in the human brain

  • Regular Paper
  • Published:
Acta Neuropathologica Aims and scope Submit manuscript

Abstract

Autosomal dominant optic atrophy (adOA) is the most prevalent hereditary optic neuropathy with moderate to severe visual field loss and loss of retinal ganglion cells. The majority of cases of adOA is associated with mutations in the OPA1 gene. Northern blot analyses showed that OPA1 is expressed in all tissues examined, with the highest transcript level in the retina and in the brain. Here we addressed the cell type-specific expression of the OPA1 protein in human brain sections using immunohistochemical techniques and Western blotting. We studied OPA1 expression in normal cerebellum and various cerebral CNS tissue specimen of different areas obtained at autopsy from patients with no reported neurological symptoms or diseases and no neuropathological alterations using a polyclonal antibody raised against a C-terminal peptide of OPA1. We found OPA1 expression in somata and dendrites of neurons of the layers II–VI of the motor cortex and frontal brain. In the cerebellar cortex, OPA1 expression was detected in the Purkinje cell layer, in the granule cell layer and in the molecular layer. Double-labeling experiments showed also OPA1 expression in GFAP-positive astrocytes. Since mutations in the OPA1 gene specifically causes optic atrophy and occurrence of cerebral anomalies in adOA patients is not characteristic, this finding may suggest different cellular susceptibility of OPA1 in brain and retinal tissues.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Aijaz S, Erskine L, Jeffery G, Bhattacharya SS, Votruba M (2004) Developmental expression profile of the optic atrophy gene product: OPA1 is not localized exclusively in the mammalian retinal ganglion cell layer. Invest Ophthalmol Vis Sci 45:1667–1673

    Article  Google Scholar 

  2. Alexander C, Votruba M, Pesch UEA, Thiselton DL, Mayer S, Moore A, Rodriguez M, Kellner U, Leo-Kottler B, Auburger G, Bhattacharya SS, Wissinger B (2000) OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28. Nat Genet 26:211–215

    Article  Google Scholar 

  3. Delettre C, Lenaers G, Griffoin JM, Gigarel N, Lorenzo C, Belenguer P, Pelloquin L, Grosgeorge J, Turc-Carel C, Perret E, Astarie-Dequeker C, Lasquellec L, Arnaud B, Ducommun B, Kaplan J, Hamel CP (2000) Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nat Genet 26:207–210

    Article  Google Scholar 

  4. Delettre C, Griffoin JM, Kaplan J, Dollfus H, Lorenz B, Faivre L, Lenaers G, Belenguer P, Hamel CP (2001) Mutation spectrum and splicing variants in the OPA1 gene. Hum Genet 109:584–591

    Article  Google Scholar 

  5. Gernet H (1964) Hereditäre Opticusatrophie in Kombination mit Taubheit. Ber Zusammenkunft Dtsch Opthalmol Ges 65:545–547

    Google Scholar 

  6. Guan K, Farh L, Marshall TK, Deschenes RJ (1993) Normal mitochondrial structure and genomic maintenance in yeast requires the dynamin-like product of the MGM1 gene. Curr Genet 24:141–148

    Article  Google Scholar 

  7. Hoyt CS (1980) Autosomal dominant optic atrophy: a spectrum of disability. Ophthalmology 87:245–251

    Google Scholar 

  8. Jaeger W (1954) Dominant vererbte Optikusatrophie. Albrecht von Graefes Arch Ophthalmol 155:457–484

    Article  Google Scholar 

  9. Johnston RL, Seller MJ, Behnam JT, Burdon MA, Spalton DJ (1999) Dominant optic atrophy. Refining the clinical diagnostic criteria in light of genetic linkage studies. Ophthalmology 106:123–128

    Article  Google Scholar 

  10. Joseph R, David JB (1958) Dominantly inherited optic atrophy. Br J Opthalmol 42:413–424

    Google Scholar 

  11. Kjer B, Eiberg H, Kjer P, Rosenberg T (1996) Dominant optic atrophy mapped to chromosome 3q region. Acta Ophthalmol Scand 74:3–7

    Google Scholar 

  12. Kjer P (1956) Infantile optic atrophy with dominant transmission. Dan Med Bull 3:135–141

    Google Scholar 

  13. Kjer P, Jensen OA, Klinken L (1983) Histopathology of eye, optic nerve and brain in a case of dominant optic atrophy. Acta Opthalmol 61:300–312

    Google Scholar 

  14. Kok-Van Alphen CC (1970) Four families with the infantile form of optical atrophy. Acta Ophthalmol (Copenh) 48:905–916

    Google Scholar 

  15. Lorenz B (1994) Hereditary optic atrophy. Ophthalmologe 91:831–850

    Google Scholar 

  16. Lyle WM (1990) Genetic risks. University of Waterloo Press, Waterloo

  17. Matsuoka I, Suzuki Y, Defer N, Nakanishi H, Hanoune J (1997) Differential expression of type I, II, and V adenylyl cyclase gene in the postnatal developing rat brain. J Neurochem 68:498–506

    Google Scholar 

  18. Michal S, Ptasinska-Urbanska M, Mitkiewicz-Bochenek W (1968) Atrophie optique hérédo-familiale dominante associée à la surdi-mutité. Ann Oculist (Paris) 201:431–435

    Google Scholar 

  19. Minich T, Yokota S, Dringen R (2003) Cytosolic and mitochondrial isoforms of NADP+-dependent isocitrate dehydrogenases are expressed in cultures rat neurons, astrocytes, oligodendrocytes and microglial cells. J Neurochem 86:605–614

    Article  Google Scholar 

  20. Misaka T, Miyashita T, Yoshihiro Kubo (2002) Primary structure of a dynamin-ralated mouse mitochondrial GTPase and its distribution in brain, subcellular localization, and effect on mitochondrial morphology. J Biol Chem 277:15834–15842

    Article  Google Scholar 

  21. Mittelbronn M, Dietz K, Schluesener HJ, Meyermann R (2001) Local distribution of microglia in the normal adult human central nervous system differs by up to one order of magnitude. Acta Neuropathol 101:249–255

    Google Scholar 

  22. Mizushima K, Miyamoto Y, Tsukahara F, Hirai M, Sakaki Y, Ito T (2000) A novel G-protein-coupled receptor gene expressed in the striatum. Genomics 69:324–321

    Article  Google Scholar 

  23. Olichon A, Emorine LJ, Descoins E, Pelloquin L, Brichese L, Gas N, Guillou E, Delettre C, Valette A, Hamel C, Ducommun B, Lenaers G, Belenguer P (2002) The human dynamin-related protein OPA1 is anchored to the mitochondrial inner membrane facing the inter-membrane space. FEBS Lett 523:171–176

    Article  Google Scholar 

  24. Pelloquin L, Belenguer P, Menon Y, Ducommun B (1998) Identification of a fission yeast dynamin-related protein involved in mitochondrial DNA maintenance. Biochem Biophys Res Commun 251:720–726

    Article  Google Scholar 

  25. Perkins GA, Renken CW, Frey TG, Ellisman MH (2001) Membrane architecture of mitochondria in neurons of the central nervous system. J Neurosci Res 66:857–865

    Article  Google Scholar 

  26. Pesch UEA, Leo-Kottler B, Mayer S, Jurklies B, Kellner U, Apfelstedt-Sylla E, Zrenner E, Wissinger B (2001) OPA1 mutations in patients with autosomal dominant optic atrophy and evidence for semi-dominant inheritance. Hum Mol Genet 10:1359–1368

    Article  Google Scholar 

  27. Pesch UEA, Fries JE, Bette S, Kalbacher H, Wissinger B, Alexander C, Kohler K (in press) Opa1, the disease gene for autosomal dominant optic atrophy, is specifically expressed in ganglion cells and intrinsic neurons of the retina. Invest Ophthalmol Vis Sci

  28. Votruba M, Moore AT, Bhattacharya SS (1998) Clinical features, molecular genetics and pathophysiology of dominant optic atrophy. J Med Genet 35:793–800

    Google Scholar 

  29. Satoh M, Hamamoto T, Seo N, Kagawa Y, Endo H (2003) Differential sublocalization of the dynamin-related protein OPA1 isoforms in mitochondria. Biochem Biophys Res Commun 300:482–493

    Article  Google Scholar 

Download references

Acknowledgements

The authors are grateful to Dr. Konrad Kohler and Simone Schimpf for fruitful discussion. This work was supported by the Deutsche Forschungsgemeinschaft (WI 1189/4-1).

Author information

Authors and Affiliations

  1. Molecular Genetics Laboratory, University Eye hospital, Tübingen, Germany

    Stefanie Bette & Bernd Wissinger

  2. Institute of Brain Research, University of Tübingen, Calwerstr. 3, 72076, Tübingen, Germany

    Holger Schlaszus, Richard Meyermann & Michel Mittelbronn

Authors
  1. Stefanie Bette
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Holger Schlaszus
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bernd Wissinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Richard Meyermann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michel Mittelbronn
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michel Mittelbronn.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bette, S., Schlaszus, H., Wissinger, B. et al. OPA1, associated with autosomal dominant optic atrophy, is widely expressed in the human brain. Acta Neuropathol 109, 393–399 (2005). https://doi.org/10.1007/s00401-004-0970-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00401-004-0970-8

Keywords

Search

Navigation