2005 Fiscal Year Final Research Report Summary
Pathogenic analysis for autoimmune and hereditary skin diseases due to abnormality of desmosomes
| Project/Area Number |
14370264
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Kurume University School of Medicine |
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Principal Investigator |
HASHIMOTO Takashi Kurume University School of Medicine, Professor, 医学部, 教授 (20129597)
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| Co-Investigator(Kenkyū-buntansha) |
YASUMOTO Shinichiro Kurume University School of Medicine, Associate Professor (10220162)
KUSUHARA Masahiro Kurume University School of Medicine, Assistant Professor (40195441)
KARASHIMA Tadashi Kurume University School of Medicine, Assistant Professor (70211175)
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| Project Period (FY) |
2002 – 2005
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| Keywords | desmosome / autoimmune / mutation / plakophilin / desmocollin / envoplakin / periplakin / desmoyokin |
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| Research Abstract |
By immunofluorescence using COS-7 cells transfected with cDNAs of human desmocollins 1-3, we have shown that some pemphigus sera contained IgA antibodies reactive with desmocollins. There are two subtypes of IgA pemphigus, IEN type and SPD type. By immuno-electron microscopic study, we have shown that IgA antibodies of SPD type IgA pemphigus reacted with desmosomal areas, whereas IgA antibodies of IEN type IgA pemphigus reacted with non-desmosomal areas. We have shown that most of the sera of IgG/IgA pemphigus had IgG and IgA antibodies reactive with Dsg1/Dsg3 and Dsc1. In addition, by immuno-electron microscopic study, it is shown that these sera reacted with desmosomal areas. We have examined a large family with patients showing acantholytic blister above the basal layer. First, we examined desmoglein 3 gene, but we could not find a mutation. However, we have found a mutation in the ATP2A2 gene, encoding SERCA2, the causative gene of Darier disease. In a patient showing superficial blister formation in the epidermis, we have not detected any mutations in the genes of desmosomal proteins. In stead, in this patient, we have found a mutation in the C-terminal area of keratin 1 gene. We have produced various recombinant proteins of envoplakin and periplakin. By immunoblotting using theses recombinant proteins, we have shown that most paraneoplastic pemphigus patients reacted with various domains of envoplakin and periplakin. We have succeeded to produce knockout mice of desmoyokin. We could not find any morphological abnormality in the desmosomes. In addition,. the cell culture from the knockout mice did not show an abnormal cell adhesion.
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Research Products
(9 results)
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[Book] 今日の皮膚疾患治療指針2002
Author(s)
橋本 隆, 編集:齊田俊明, 塩原哲夫, 宮地良樹, 渡辺晋一
Total Pages
789
Publisher
医学書院
Description
「研究成果報告書概要(和文)」より
