Severe Combined Immunodeficient(SCID) Mice As Animal Models for Human Echinococcosis

严重联合免疫缺陷（SCID）小鼠作为人类包虫病的动物模型

• 批准号: 15500295
• 负责人: NAKAYA Kazuhiro
• 金额: $ 2.43万
• 依托单位: Asahikawa Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15500295/
• 关键词: Immunodeficient (SCID) mouse; NOD; Shi-scid; Echinococcus multilocularis; metacestode; intermediate host; Animal model; multivesiculation; protoscolex formation; Shi-scid; 病態モデルマウス; 免疫不全; NOD-scid; Alveolar echinococcosis; 転移; Em 18

At first, two strains of sever combined immune-deficiency mice, C.B-17/Icr-scid and NOD/Shi-scid were compared with the sensitivity to Echinococcus multilocularis metacestode. At post infection 9 and 12weeks, the developed metacestode of two strains infra peritoneal cavities were weighed and compared. NOD/Shi-scid showed more high degree weight than C.B-17/Icr-scid at both points of weeks. It was suggested that scid-gene, declines of macrophage function and compliment activity were influenced together.So, development and growth of metacestode in NOD/Shi-scid were observed in detail. At post infection 1,2,3 weeks, between NOD/Shi-scid and control NOD/Shi-+/+ mice, there were no defferences both weight and morphologies of metacestodes. NOD/Shi-+/+ mice were not revealed for rEm-18 antibody in these periods. It was considered that so-called prepatent period which antibody was not yet producted in host immune system. After post infection 6 weeks, in NOD/Shi-scid mice, multivesiculation and formation of protoscolex were rapidly proceeded. NOD/Shi-scid mice showed striking torelance for the parasite development and growth. It was suggested that NOD/Shi-scid mouse would be a model for human echinococcosis.And moreover, it was attempted of quantification of multivesiculation and protoscolex formation of the parasite between NOD/Shi-scid and NOD/Shi-+/+ mice. After post infection 6 weeks, in NOD/Shi-scid mice, index of multivesiculation and protoscolex formation suddenly increased. While in NOD/Shi-+/+ mice, in spite of spread of parasite and inflamated fucus, index of multivesicelation was decreased for not changed number of vesicular. Index of protoscolex also increased more in NOD/Shi-scid mice than in NOD/Shi-+/+ mice. It was expected that index methods of these parasite development or growth was usefullness in evaluation of host sensitivity and drug efficacy, estimate of infectious point.

首先比较了两种严重联合免疫缺陷小鼠C.B-17/Icr-scid和NOD/Shi-scid对多房棘球绦虫的敏感性。感染后9周和12周，对两种菌株腹腔下发育的后绦虫进行称重并比较。在两周的两个时间点，NOD/Shi-scid 显示出比 C.B-17/Icr-scid 更高的程度权重。提示scid基因与巨噬细胞功能下降和补体活性共同影响。因此,对NOD/Shi-scid中后绦虫的发育和生长进行了详细观察。感染后1、2、3周，NOD/Shi-scid小鼠和对照NOD/Shi-+/+小鼠之间，后绦虫的重量和形态均无差异。在此期间，NOD/Shi-+/+ 小鼠未发现 rEm-18 抗体。认为宿主免疫系统尚未产生抗体的所谓潜伏期。感染后6周后，NOD/Shi-scid小鼠中，多泡和原头节的形成迅速进行。 NOD/Shi-scid 小鼠对寄生虫的发育和生长表现出惊人的耐受性。有人建议NOD/Shi-scid小鼠可以作为人类包虫病的模型。此外，还尝试定量NOD/Shi-scid和NOD/Shi-+/+小鼠之间寄生虫的多囊泡和原头节形成。感染后6周后，NOD/Shi-scid小鼠的多泡指数和原头节形成突然增加。而在NOD/Shi-+/+小鼠中，尽管寄生虫扩散且墨角藻发炎，但多囊泡指数下降，囊泡数量没有变化。 NOD/Shi-scid 小鼠的原头节指数也比 NOD/Shi-+/+ 小鼠增加更多。预计这些寄生虫发育或生长的指标方法可用于评估宿主敏感性和药物功效、估计感染点。

项目成果

Molecular cloning, expression, and serological evaluation of an, 8-kilodalton subunit of antigen B from Echinococcus multilocularis

• DOI: 10.1128/jcm.42.3.1082-1088.2004
• 发表时间: 2004-03-01
• 期刊: JOURNAL OF CLINICAL MICROBIOLOGY
• 影响因子: 9.4
• 作者: Mamuti, W;Yamasaki, H;Ito, A
• 通讯作者: Ito, A

伊藤亮, 石川裕司, 北田正博, 中谷和宏, 笹嶋唯博(2003): "肺エキノコックス症"呼吸. 22・1. 56-60 (2003)

Ryo Ito、Yuji Ishikawa、Masahiro Kitada、Kazuhiro Nakatani、Yuhiro Sasashima (2003)：“肺包虫病”22・1 (2003)。

Magnetic resonance imaging and immunoblot analyses in rats with experimentally induced cerebral alveolar echinococcosis.

• 发表时间: 2003-12
• 期刊: Comparative medicine
• 影响因子: 0.8
• 作者: T. Asanuma;Yukari Matsumoto;M. Takiguchi;O. Inanami;M. Nakao;K. Nakaya;A. Ito;A. Hashimoto;M. Kuwabara

Ito A, Sako Y, Yamasaki H, Mamuti W, Nakaya K, Nakao M, Ishikawa Y.: "Development of Em18-immunoblot and Em18-ELISA for specific diagnosis of alveolar echinococcosis"Acta Trop.. 85・2. 173-182 (2003)

Ito A、Sako Y、Yamasaki H、Mamuti W、Nakaya K、Nakao M、Ishikawa Y.：“开发用于特异性诊断肺泡包虫病的 Em18 免疫印迹和 Em18-ELISA”Acta Trop.. 85・2。 (2003)

Echinococcus multilocularis confirmed from Kunashiri Island, 15km far from Hokkaido, Japan

距离日本北海道15公里的国后岛确诊多房棘球绦虫

• 发表时间: 2005
• 期刊: Am J Trop Med Hyg. 72(3)
• 作者: Satoh M;Nakaya K;Nakao M;Xiao N;Yamasaki H;Naitoh Y;Kondo S;Kobayashi M;Ohtaishi N;Ito A.
• 通讯作者: Ito A.