Identification of Modifier Genes for Atopic Dermatitis Development
| Project/Area Number |
18604010
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
アレルギー
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| Research Institution | RIKEN |
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Principal Investigator |
YOSHIDA Hisahiro RIKEN, RIKEN, Laboratory for Immunogenetics, Team Leader (20281090)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,240,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥540,000)
Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2006: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | atopic dermatitis / signal transduction molecule / point mutation / bone marrow chimerism / developmental mechanism of dermatitis / RNA microarray / skin barrier / modifier genes for atooic dermatitis / ENUミュタジェネシス / 飼育環境 / 骨髄キメラ / 皮膚バリア / 血液細胞 / サイトカイン信号伝達 / 遺伝子変異 / ランダムミュタジェネシス / 環境因子 / 皮膚のバリア機能 |
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| Research Abstract |
An atopic dermatitis model mutant mouse was identified as an autosomal recessive mutant in Ethyl Nitomso Urea induced random mutagenesis screen by their phenotype. In this offspring analysis in C57B1/6 background, we have identified the symptom variation among a littermates correlated with high serum IgE level, and in addition there were some other animals having high serum IgE but atopic dermatitis. This finding suggested that there are some other modifier mutation, which may have effect on AD oceunrenoe and symptoms. Then, we have started to detect two independent responsible genes br atopic dermatitis phenotype or serum IgE elevation found in the same mutant pedigree by chance. We have tried to map the responsible locus by means of genetic mapping with C3H/HeJ background and confirmed the inheritance of both phenotype in expected Mendelian rate in offspring. Dermatitis responsible mutation resulted in the point mutation of a signal transdu Lion molecule which have various roles in cytokine or growth factor signaling, however, high serum IgE mutation locus was unable to identify. Since the background bias among each mouse strain is quite different on Th1 or Th2 tendency of the animal immune condition, C3H/HeJ background might mask the IgE high phenotype. Even with QTL analysis, it was impossible to detect the second mutation loci.
After bone marrow chimerism experiment, we found the cause of AD occurrence in skin tissue but not in bone marrow cells of dermatitis mutant mouse. Microarray analysis of mutant ear skin babe disease onset, we have found 12 independent genes are expressed higher in mutant skin than wild type. A half of them are reported to have the roles in maintenance of the skin barrier function These genes could be the modifier genes for AD disease occurrence and symptoms.
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Report
(3 results)
Research Products
(12 results)
