Reduction of chromatin assembly factor 1 p60 and C21orf2 protein, encoded on chromosome 21, in Down Syndrome brain

  • K. S. Shim
  • J. M. Bergelson
  • M. Furuse
  • V. Ovod
  • T. Krude
  • G. Lubec
Part of the Journal of Neural Transmission Supplement 67 book series (NEURAL SUPPL, volume 67)


Trisomy 21 (Down syndrome, DS) is the most common genetic cause of mental retardation, resulting from triplication of the whole or distal part of human chromosome 21. Overexpression of genes located on chromosome 21, as a result of extra gene load, has been considered a central hypothesis for the explanation of the DS phenotype. This gene dosage hypothesis has been challenged, however. We have therefore decided to study proteins whose genes are encoded on chromosome 21 in brain of patients with DS and Alzheimer’s disease (AD), as all patients with DS from the fourth decade show Alzheimer-related neuropathology. Using immunoblotting we determined Coxsackievirus and adenovirus receptor (CAR), Claudin-8, C21orf2, Chromatin assembly factor 1 p60 subunit (CAF-1 p60) in frontal cortex from DS, AD and control patients. Significant reduction of C21orf2 and CAF-1 p60, but comparable expression of CAR and claudin-8 was observed in DS but all proteins were comparable to controls in AD, even when related to NSE levels to rule out neuronal cell loss or actin to normalise versus a housekeeping protein. Reduced CAF-1 p60 may reflect impaired DNA repair most probably due to oxidative stress found as early as in fetal life continuing into adulthood. The decrease of C21orf2 may represent mitochondrial dysfunction that has been reported repeatedly and also data on CAR and claudin-8 are not supporting the gene-dosage hypothesis at the protein level. As aberrant expression of the four proteins was not found in brains of patients with AD, decreased CAF and C21orf2 can be considered specific for DS.


Down Syndrome Nucleosome Assembly Down Syndrome Patient Chromatin Assembly Factor Adenovirus Receptor 
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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • K. S. Shim
    • 1
  • J. M. Bergelson
    • 2
  • M. Furuse
    • 3
  • V. Ovod
    • 4
  • T. Krude
    • 5
  • G. Lubec
    • 1
    • 6
  1. 1.Department of PediatricsUniversity of ViennaViennaAustria
  2. 2.Division of Immunologic and Infectious DiseasesChildren’s Hospital of PhiladelphiaPhiladelphiaUSA
  3. 3.Department of Cell Biology, Faculty of MedicineKyoto UniversityKyotoJapan
  4. 4.MAbs Development and ProductionFIT Biotech Oyj PlcTampereFinland
  5. 5.Department of ZoologyUniversity of CambridgeCambridgeUK
  6. 6.CChem, FRSC (UK), Department of PediatricsUniversity of ViennaViennaAustria

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