The disease model of the new discovery atopic dermatitis mouse and the positional cloning of the responsibility gene
| Project/Area Number |
16390292
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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 |
膠原病・アレルギー・感染症内科学
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| Research Institution | Saitama Cancer Center |
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Principal Investigator |
MATSUSHIMA Yoshibumi Saitama Cancer Center, Research Institute for Clinical Oncology, 研究員 (10094955)
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| Project Period (FY) |
2004 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2005: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | snontaneous / mouse / atopic dermatitis / Traf3ip2 / congenic / disease model / molossinus / IgE / コンジェニック / 日本産野生マウス / 掻痒行動 / マスト細胞 / コンジェニックマウス |
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| Research Abstract |
Atopic dermatitis (AD) is a hereditary pruritic chronic relapsing eczematous dermatitis resulted from complex interactions between genetic and environmental factors, and is frequently associated with elevated levels of serum IgE. While much effort was made to elucidate the pathogenesis, it remains to be elusive and responsible genes are not identified. Hence, establishment of animal models for hereditary AD is an urgent issue: We here report the establishment of a new mouse model, named Nippon atopic dermatitis (NAD) mice, and the mapping of responsible gene.
1. NAD mice were derived from KOR mice, an inbred strain of Mus musclus molossinus, and their phenotype was transmitted in an autosomal recessive manner. The phenotype of NAD mice kept in SPF environment first appeared as edematous skin change at eyelids at the age of 4-5 weeks with elevation of serum IgE. The edema spread to other face regions, head and forefoot ; the affected skin is infiltrated with mast cell and eventually developed erosion, ulceration and loss of hairs. These clinical characteristics are distinct from those of NC mice, another mouse model of AD : Breeding test revealed that the alleles of NAD and NC mice are different.
2. Linkage analysis using F2 between NAD and BALB/c revealed that the responsible gene localizes on chromosome 10 close to D10Mit53 and D10Mit109. Interestingly, human chromosomal region syntenic ton this region, 6q22-23, contains the INFgR and TNFaIP3 genes, which may be responsible genes for AD. Further study of NAD mice will contribute to elucidate the pathogenesis of AD.
3. A novel mutant that showed human atopic dermatitis-like phenotypes was found in a colony of the inbred mouse strain KOR. Positional cloning revealed that the mouse homologue of human Traf3ip2 protein, carried a single point mutation leading to the substitution of^214glutamine for nonsense codon. This indicated that Traf3ip2 played an important role in the homeostasis of epithelial cells and B cells
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Report
(4 results)
Research Products
(4 results)
