Journal of Inherited Metabolic Disease

, Volume 34, Issue 5, pp 1061–1068 | Cite as

Thymic involution and corticosterone level in Sandhoff disease model mice: new aspects the pathogenesis of GM2 gangliosidosis

  • Kazuhiko Matsuoka
  • Daisuke Tsuji
  • Takao Taki
  • Kohji Itoh
Original Article


Sandhoff disease (SD) is a lysosomal disease caused by a mutation of the HEXB gene associated with excessive accumulation of GM2 ganglioside (GM2) in lysosomes and neurological manifestations. Production of autoantibodies against the accumulated gangliosides has been reported to be involved in the progressive pathogenesis of GM2 gangliosidosis, although the underlying mechanism has not been fully elucidated. The thymus is the key organ in the acquired immune system including the development of autoantibodies. We showed here that thymic involution and an increase in cell death in the organ occur in SD model mice at a late stage of the pathogenesis. Dramatic increases in the populations of Annexin-V+ cells and terminal deoxynucletidyl transferase dUTP nick end labeling (TUNEL) + cells were observed throughout the thymuses of 15-week old SD mice. Enhanced caspase-3/7 activation, but not that of caspase-1/4, -6 ,-8, or −9, was also demonstrated. Furthermore, the serum level of corticosterone, a potent inducer of apoptosis of thymocytes, was elevated during the same period of apoptosis. Our studies suggested that an increase in endocrine corticosterone may be one of the causes that accelerate the apoptosis of thymocytes leading to thymic involution in GM2 gangliosidosis, and thus can be used as a disease marker for evaluation of the thymic condition and disease progression.


Corticosterone Enzyme Replacement Therapy Thymic Involution Gangliosidosis Thymus Weight 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by the Program the Promotion of Fundamental Studied Health Sciences of the National Institute of Biomedical Innovation (NIBIO) (Osaka, Japan), and a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.


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Copyright information

© SSIEM and Springer 2011

Authors and Affiliations

  • Kazuhiko Matsuoka
    • 1
  • Daisuke Tsuji
    • 1
    • 3
  • Takao Taki
    • 2
  • Kohji Itoh
    • 1
    • 3
  1. 1.Department of Medicinal Biotechnology, Institute for Medicinal Research, Graduate School of Pharmaceutical SciencesThe University of TokushimaTokushimaJapan
  2. 2.Institute of Biomedical InnovationOtsuka Pharmaceutical Co., Ltd.Kawauchi-choJapan
  3. 3.NIBIOOsakaJapan

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