AIE-75 gene : with special reference to the differentiation of mucosal epithelial cells and the regulation of gene expression
AIE-75 gene : with special reference to the differentiation of mucosal epithelial cells and the regulation of gene expression
批准号:
14370237
负责人:
KOBAYASHI Kunihiko
金额:
$9.41万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B)
财政年份:
2002
资助国家:
日本
项目状态:
已结题
起止时间:
2002 至 2003
中文摘要
自身免疫性肠病是一种罕见的疾病,其特征是严重和顽固性腹泻和循环中存在的抗肠细胞自身抗体。我们已经确定了自身免疫性肠病相关的75 kDa抗原(AIE-75)作为疾病的候选自身抗原,其分布于小肠和近端肾小管的刷状缘。AIE-75的分布仅限于绒毛的顶端部位,表明其表达以细胞周期或成熟依赖的方式进行调节。为了探讨这一点,我们用荧光素酶分析了AIIE-75基因启动子区的顺式元件,发现转录起始位点上游-9 ~-63碱基参与了该基因表达的负调控,并与其他研究组合作证实了抗AJE-75抗体在自身免疫性肠病中的特异性和敏感性。此外,我们还发现了一种肌动蛋白结合蛋白villin,它是另一种与该疾病相关的自身抗原。AIE-75被发现是IC型Usher综合征的一个致病基因,该综合征以耳聋和视网膜病变为特征。事实上,AIE-75也在内耳和视网膜的上皮细胞中表达。我们发现ALE-75参与视网膜感光细胞与钙粘蛋白23和肌球蛋白VII的组装,但AIE-75的表达与这两种蛋白的表达无关。X连锁综合征(IPEX),其原因是叉头翅螺旋转录因子FOXP 3突变。我们在一例轻度IPEX患者中发现了FOXP 3的一个新突变T1117 G。
英文摘要
Autoimmune enteropathy is a rare disease characterized by severe and refracrory diarrhea and the presence of circulating ants-enterocyte autoantibody. We have identified autoimmune enteropathy-related 75 kDa antigen (AIE-75) as a candidate autoantigen in the disease, which distributes to the brush border of both the small intestine and proximal renal tubulus. The distribution of AIE-75 is limited to the apical site of the villi, suggesting that the expression is regulated in cell cycle-or maturation-dependent manners. To approach this, we analyzed cis-element of the promotor region of AIIE-75 gene using luciferase assay, and found that -9 to -63 bases upstream of the transcription initiation site is involved in he negative regulation of the gene expression.The specificity and sensitivity of anti-AJE-75 antibody in autoimmune enteropathy were confirmed in collaboration with other groups. Furthermore, we identified an actin-binding protein, villin, as another autoantigen related to the disease.AIE-75 was found to be a responsible gene for Usher's syndrome type IC which is characterized by deafness and retinopathy. Indeed, AIE-75 was also expressed in both epithelial cells of the inner ear and retina. We found that ALE-75 is involved in the assembly of photoreceptor with cadherin 23 and myosin VII in the retina, but that the expression of AIE-75 is independent of the expression of the both proteins.Some cases of autoimmune enteropathy are inherited in an X-linked manner, named immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) of which cause is the mutation of a forkhead winged helix transcription factor, FOXP3. We found a novel mutation of FOXP3, T1117G, in a mild case of IPEX.
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Chintalacharuvu et al.: "Cysteine Residues Required for the Attachment of the Light chain in human IgA2"J. Immunol.. 169. 5072-5077 (2002)
Chintalacharuvu 等人:“人 IgA2 中轻链附着所需的半胱氨酸残基”J。
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Clintalacharuvu., et al.: "Cysteine Residues Required for the Attachment of the Light chain in human IgA2."J.Immunol.. 169. 5072-5077 (2002)
Clintalacharuvu., et al.:“人 IgA2 中轻链附着所需的半胱氨酸残基。”J.Immunol.. 169. 5072-5077 (2002)
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Nieves, DS, et al.: "Dermatologic and Immunologic Findings in the Immune Dysregulation, Polyendorcrinopathy, Enteropathy, X-linked Syndrome."Arch.Dermatol.. (In press).
Nieves, DS 等人:“免疫失调、多内分泌腺病、肠病、X 连锁综合征的皮肤病学和免疫学发现”。Arch.Dermatol..(正在出版)。
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Iwata A, et al.: "Cloning and expression tortoise (Trachemys scripta) immunoglobulin Joiningu (J)-chain cDNA."Immunogenetics. 54. 513-519 (2002)
Iwata A 等人:“克隆和表达陆龟 (Trachemys scripta) 免疫球蛋白 Joiningu (J)-链 cDNA。”免疫遗传学。
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共 23 条
Study on dynamics in the prevention of root fractures in abutment teeth of the fixed partial denture
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批准号:19592221
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$2.66万
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财政年份:2007
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负责人:KOBAYASHI Kunihiko
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依托单位:
Study of a novel autoantigen related to autoimmune enteropathy with renal tubular dysfunction
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批准号:12470162
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$8.9万
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财政年份:2000
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负责人:KOBAYASHI Kunihiko
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依托单位:
Designing an Intercultural Syllabus
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批准号:11610301
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$1.34万
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财政年份:1999
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负责人:KOBAYASHI Kunihiko
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依托单位:
A Study on Abutment Forms and materials of Restorations utilizing Adhesion
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批准号:11671919
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$2.3万
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财政年份:1999
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负责人:KOBAYASHI Kunihiko
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依托单位:
Studies on human osteopontin : isolation and characterization of osteopontin in milk and serum.
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批准号:09557062
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$5.89万
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财政年份:1997
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负责人:KOBAYASHI Kunihiko
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依托单位:
STUDIES ON CALCIUM BINDING PROTEIN,OSTEOPONTIN,ITS DIAGNOSTIC AND THERAPEUTIC APPLICATION FOR BONE DISORDERS.
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批准号:07557061
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项目类别:Grant-in-Aid for Scientific Research (A)
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资助金额:$7.62万
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财政年份:1995
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负责人:KOBAYASHI Kunihiko
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依托单位:
STUDIES ON MANNOSE-BINDING-PROTEIN (MBP) ; WITH SPECIAL REFERENCE TO COMPLEMENT ACTIVATION AND REGULATION,AND ITS DEPOSITION IN RENAL TISSUES
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批准号:07457176
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项目类别:Grant-in-Aid for Scientific Research (B)
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资助金额:$4.8万
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财政年份:1995
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负责人:KOBAYASHI Kunihiko
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依托单位:
A study on Adhesion Mechanism between Adhesive resin and Dentin
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批准号:06671938
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项目类别:Grant-in-Aid for General Scientific Research (C)
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资助金额:$1.41万
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财政年份:1994
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负责人:KOBAYASHI Kunihiko
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依托单位:
A Study of Attrition Caused by Various Restorative Materials
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批准号:03670907
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项目类别:Grant-in-Aid for General Scientific Research (C)
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资助金额:$1.34万
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财政年份:1991
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负责人:KOBAYASHI Kunihiko
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依托单位:
Human serum mannose-binding protein: its function and a possible application to the clinical use.
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批准号:03454505
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项目类别:Grant-in-Aid for General Scientific Research (B)
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资助金额:$4.22万
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财政年份:1991
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负责人:KOBAYASHI Kunihiko
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依托单位:
Formation of Native-Type Collagen Fibrils by Cultured Fibroblasts.
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批准号:01570008
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项目类别:Grant-in-Aid for General Scientific Research (C)
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资助金额:$1.28万
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财政年份:1989
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负责人:KOBAYASHI Kunihiko
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依托单位:
Development of a simple procedure for the isolation of secretory IgA by lectin affinity chromatography and its clinical application.
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批准号:61480217
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项目类别:Grant-in-Aid for General Scientific Research (B)
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资助金额:$2.37万
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财政年份:1986
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负责人:KOBAYASHI Kunihiko
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依托单位:
海外基金