2013 Fiscal Year Final Research Report
Elucidation of the pathophysiology of the Nakajo-Nishimura syndrome which is hereditary proteasome disability and trial of the enzyme replacement therapy
| Project/Area Number |
24791170
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Dermatology
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| Research Institution | Wakayama Medical University |
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Principal Investigator |
KUNIMOTO Kayo 和歌山県立医科大学, 医学部, 助教 (10438278)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | 中條-西村症候群 / PSMB8 / プロテアソーム |
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| Research Abstract |
Nakajo-Nishimura syndrome is a autosomal recessively-inherited disorder that onsets in infancy with pernio-like rashes and gradually develops into partial lipodystrophy. A homozygous mutation of the PSMB8 immunoproteasome subunit gene has been identified to be responsible for NNS. Abolished MHC class I expression and CD8 T cell proliferation in PSMB8-knockout mice have been reported. In this study, expression and functional abnormality of MHC (class I and II) has been examined using immortalized B cells and peripheral blood mononuclear cells obtained from NNS patients. Expression of HLA-DR was defective in NNS-imB cells, but HLA-DR expression was observed intracellularly in NNS-imB/PBMC. Presence of some structural abnormality is suspected in HLA-DR.There is a possibility that a hitchhiking mutation in the HLA-DR gene causes a structural change, because the PSMB8 gene is located in the MHC class II region. Hitchhiking mutation in the HLA-DR gene was not detected in gene analysis.
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