2003 Fiscal Year Annual Research Report

cDNAマイクロアレイによるトキソプラズマ性網脈絡膜炎発症機序の遺伝的解析

Research Project

Project/Area Number	14571657
Research Institution	Chiba University
Principal Investigator	野呂瀬一美千葉大学, 大学院・医学研究院, 助手 (30156244)
Co-Investigator(Kenkyū-buntansha)	岩倉洋一郎東京大学, 医科学研究所, 教授 (10089120) 矢野明彦千葉大学, 大学院・医学研究院, 教授 (20135122) 青才文江千葉大学, 大学院・医学研究院, 助教授 (80150316)
Keywords	トキソプラズマ性網脈絡膜炎 / マイクロアレイ / ブドウ膜炎 / インターフェロンガンマ / 網膜血管炎
Research Abstract	1.細胞内寄生体トキソプラズマにより引き起こされるトキソプラズマ性網脈絡膜炎は、インターフェロンガンマ(IFN-γ)がその発症機序に関与している(Norose et al. J Parasitol 87:447,2001)。今回の研究では、多数の遺伝子の発現状態やゲノムの変異を大規模に同時並行で検出できるcDNAマイクロアレイを用いてトキソプラズマ性網脈絡膜炎に関与する多数の遺伝子の発現調整機構を解析した。 2.トキソプラズマ非感染正常マウスのmRNAから作成したcDNAマイクロアレイを用いて、トキソプラズマ原虫感染抵抗性マウスBALB/c野生型対BALB/cIFN-γKO(GKO)マウスおよびトキソプラズマ原虫感染抵抗性マウスBALB/c野生型対感受性マウスC57BL/6野生型の組み合わせによってトキソプラズマ原虫感染に特異的に発現変動(2倍以上あるいは1/2倍以下)する遺伝子の検索を行ったところ、b2-microglobulin, DMR-N9, spot 14,teststeronの関連遺伝子および未知遺伝子(仮称T. g. Res. X遺伝子)が得られた。現在、上記遺伝子および未知遺伝子の生化学的生物学的活性の解析を進めている。 3.さらに、トキソプラズマFukaya弱毒株のシストを野生型のトキソプラズマ感受性マウスC57BL/6およびC57BL/6由来GKOマウスに経口投与し、経時的に眼底検査を行い、網脈絡膜炎の有無を観察した結果、C57BL/6GKOマウスにおいて、感染後約10日で、蛍光眼底造影にて、網膜血管炎が認められた。 4.また、トキソプラズマ感染後、経時的に眼球を摘出し、DNAを作成し、定量的競合的(QC)-PCR法で眼内のトキソプラズマDNAを検索した結果、野生型マウスでは、網膜に、GKOマウスでは、主に虹彩、脈絡膜にトキソプラズマDNAが認められた(Norose et al. Invest Ophthalmol Vis Sci 44:4375,2003)。また、病理学的に検討したところ、野生型マウスにおいて、網膜に色素細胞や炎症性細胞の浸潤を認め、トキソプラズマのシストが存在したが、GKOマウスにおいては炎症性細胞の浸潤は認めたが、シスト形成は認めなかった。 5.トキソプラズマ性網脈絡膜炎の実験モデルで、関連する遺伝子の発現調整機構を上記cDNAマイクロアレイを用いて解析中である。

Research Products

(21 results)

All Other

All Publications (21 results)

[Publications] Piao L-X: "A quantitative assay method of Toxoplasma gondii HSP7O mRNA by quantitative competitive-reverse transcriptase-PCR."Parasitol Int. 53(1). 49-58 (2004)
[Publications] Chen M: "Induction of protective immunity by primed B-1 cells in Toxoplasma gondii-infected B cell-deficient mice"Microbiol Immunol. 47(12). 997-1003 (2003)
[Publications] Norose K: "IFN-γ-regulated Toxoplasma gondii distribution and load in the murine eye"Invest Ophthalmol Vis Sci. 44(10). 4375-4381 (2003)
[Publications] Mun H-S: "TLR2 as an essential molecule for protective immunity against Toxoplasma gondii infection"Intern Immunol. 15(9). 1081-1087 (2003)
[Publications] Mun H-S: "Pathogenicity of Toxoplasma gondii through B-2 cell-mediated downregulation of host defense responses"Microbiol Immunol. 47(7). 533-542 (2003)
[Publications] Belal US: "An animal model for establishing chemotherapy against intractable toxoplasmosis in immunocompromised hosts by the use of IFN-γ knockout mice"Jpn J Trop Med Hyg. 31(2). 83-86 (2003)
[Publications] Mohamed RM: "Induction of protective immunity by DNA vaccination with Toxoplasma gondii HSP7O, HSP3O and SAG1 genes"Vaccine. 21. 2852-2861 (2003)
[Publications] Chen M: "Correlation between the avidity maturation of anti-HSP70 IgG autoantibody and recombination activating gene expressions in peripheral lymphoid tissues of Toxoplasma gondii-infected mice"Microbiol Immunol. 47(3). 217-221 (2003)
[Publications] Chen M: "The role of anti-HSP70 autoantibody-forming V_H1-J_H1 B-1 cells in Toxoplasma gondii-infected mice."Int Immunol. 15(1). 39-47 (2003)
[Publications] Norose K: "Mapping of genes involved in murine herpes simplex virus keratitis : identification of genes and their modifiers."J Viol. 76(7). 3502-3510 (2002)
[Publications] Chen M: "Involvement of MyD88 in host defense and the down-regulation of anti-heat shock protein 70 autoantibody formation by MyD88 in Toxoplasma gondii-infected mice."J Parasitol. 88(5). 1017-1019 (2002)
[Publications] Aosai F: "Toxoplasma gondii-derived heat shock protein HSP7O functions as a B cell mitogen."Cell Stress Chaperones. 7(4). 357-364 (2002)
[Publications] Yano A: "Roles of IFN-γ on stage conversion of an obligate intracellular protozoan parasite, Toxoplasma gondii."Intern Rev Immunol. 21(4-5). 405-421 (2002)
[Publications] Naoi K: "A theoretical analysis of the relations between the risk of congenital toxoplasmosis and the annual infection rates with a convincing argument for better public intervention."Parasitol Int. 51(2). 187-194 (2002)
[Publications] Naoi K: "A new approach for the analysis of seroprevalence data : a mathematical analysis of the seroprevalence of Toxoplasma gondii infection in Hyogo prefecture (Japan) with an implication of neriodic outbreaks among young children"Jpn J Trop Med Hyg. 30(2). 99-102 (2002)
[Publications] 直井幸二: "先天性感染症に対する産婦人科医の認識調査:特に先天性トキソプラズマ症を中心とした予備的報告"日本臨床寄生虫学会雑誌. 13(1). 54-56 (2002)
[Publications] Kobayashi M: "Prevalence of toxoplasmosis in children in northeastern Brazil."Jpn J Trop Med Hyg. 30(3). 305-310 (2002)
[Publications] 矢野明彦: "トキソプラズマ症"化学療法の領域. 18(4). 481-486 (2002)
[Publications] 野呂瀬一美: "難治性トキソプラズマ性網脈絡膜炎の考察"日本臨床寄生虫学会誌. 13(1). 51-53 (2002)
[Publications] Yano A: "Progress of Medical Parasitology in Japan"Meguro Parasitological Museum. 676 (2003)
[Publications] Aosai F: "Proceedings of the 10^<th> International Congress of Parasitology-ICOPA X"Monduzzi Editore. 660 (2002)

2003 Fiscal Year Annual Research Report

cDNAマイクロアレイによるトキソプラズマ性網脈絡膜炎発症機序の遺伝的解析

Principal Investigator

野呂瀬 一美 千葉大学, 大学院・医学研究院, 助手 (30156244)

Research Products

[Publications] Piao L-X: "A quantitative assay method of Toxoplasma gondii HSP7O mRNA by quantitative competitive-reverse transcriptase-PCR."Parasitol Int. 53(1). 49-58 (2004)

[Publications] Chen M: "Induction of protective immunity by primed B-1 cells in Toxoplasma gondii-infected B cell-deficient mice"Microbiol Immunol. 47(12). 997-1003 (2003)

[Publications] Norose K: "IFN-γ-regulated Toxoplasma gondii distribution and load in the murine eye"Invest Ophthalmol Vis Sci. 44(10). 4375-4381 (2003)

[Publications] Mun H-S: "TLR2 as an essential molecule for protective immunity against Toxoplasma gondii infection"Intern Immunol. 15(9). 1081-1087 (2003)

[Publications] Mun H-S: "Pathogenicity of Toxoplasma gondii through B-2 cell-mediated downregulation of host defense responses"Microbiol Immunol. 47(7). 533-542 (2003)

[Publications] Belal US: "An animal model for establishing chemotherapy against intractable toxoplasmosis in immunocompromised hosts by the use of IFN-γ knockout mice"Jpn J Trop Med Hyg. 31(2). 83-86 (2003)

[Publications] Mohamed RM: "Induction of protective immunity by DNA vaccination with Toxoplasma gondii HSP7O, HSP3O and SAG1 genes"Vaccine. 21. 2852-2861 (2003)

[Publications] Chen M: "Correlation between the avidity maturation of anti-HSP70 IgG autoantibody and recombination activating gene expressions in peripheral lymphoid tissues of Toxoplasma gondii-infected mice"Microbiol Immunol. 47(3). 217-221 (2003)

[Publications] Chen M: "The role of anti-HSP70 autoantibody-forming V_H1-J_H1 B-1 cells in Toxoplasma gondii-infected mice."Int Immunol. 15(1). 39-47 (2003)

[Publications] Norose K: "Mapping of genes involved in murine herpes simplex virus keratitis : identification of genes and their modifiers."J Viol. 76(7). 3502-3510 (2002)

[Publications] Chen M: "Involvement of MyD88 in host defense and the down-regulation of anti-heat shock protein 70 autoantibody formation by MyD88 in Toxoplasma gondii-infected mice."J Parasitol. 88(5). 1017-1019 (2002)

[Publications] Aosai F: "Toxoplasma gondii-derived heat shock protein HSP7O functions as a B cell mitogen."Cell Stress Chaperones. 7(4). 357-364 (2002)

[Publications] Yano A: "Roles of IFN-γ on stage conversion of an obligate intracellular protozoan parasite, Toxoplasma gondii."Intern Rev Immunol. 21(4-5). 405-421 (2002)

[Publications] Naoi K: "A theoretical analysis of the relations between the risk of congenital toxoplasmosis and the annual infection rates with a convincing argument for better public intervention."Parasitol Int. 51(2). 187-194 (2002)

[Publications] Naoi K: "A new approach for the analysis of seroprevalence data : a mathematical analysis of the seroprevalence of Toxoplasma gondii infection in Hyogo prefecture (Japan) with an implication of neriodic outbreaks among young children"Jpn J Trop Med Hyg. 30(2). 99-102 (2002)

[Publications] 直井幸二: "先天性感染症に対する産婦人科医の認識調査:特に先天性トキソプラズマ症を中心とした予備的報告"日本臨床寄生虫学会雑誌. 13(1). 54-56 (2002)

[Publications] Kobayashi M: "Prevalence of toxoplasmosis in children in northeastern Brazil."Jpn J Trop Med Hyg. 30(3). 305-310 (2002)

[Publications] 矢野明彦: "トキソプラズマ症"化学療法の領域. 18(4). 481-486 (2002)

[Publications] 野呂瀬 一美: "難治性トキソプラズマ性網脈絡膜炎の考察"日本臨床寄生虫学会誌. 13(1). 51-53 (2002)

[Publications] Yano A: "Progress of Medical Parasitology in Japan"Meguro Parasitological Museum. 676 (2003)

[Publications] Aosai F: "Proceedings of the 10^<th> International Congress of Parasitology-ICOPA X"Monduzzi Editore. 660 (2002)

野呂瀬一美千葉大学, 大学院・医学研究院, 助手 (30156244)

[Publications] 野呂瀬一美: "難治性トキソプラズマ性網脈絡膜炎の考察"日本臨床寄生虫学会誌. 13(1). 51-53 (2002)