Mechanism of Resistance to MMTV Induced Mammary Tumors

MMTV诱发乳腺肿瘤的耐药机制

• 批准号: 6896126
• 负责人: Tatyana V Golovkina
• 金额: $ 14.4万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-06-01 至 2005-10-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6896126
• 关键词: adenocarcinoma; antiviral antibody; breast neoplasms; gene mutation; host organism interaction; immunogenetics; laboratory mouse; microorganism immunology; molecular cloning; mouse mammary tumor virus; neoplasm /cancer immunology; neutralizing antibody; viral carcinogenesis; virus infection mechanism; virus related neoplasm /cancer

DESCRIPTION (provided by applicant): Mouse Mammary Tumor Virus (MIMTV) is an exogenous milk-transmitted retrovirus that induces mammary gland tumors in some strains of laboratory mice. MMTV is carried from the gut of suckling pups to the mammary glands by lymphocytes. Susceptibility to exogenous MMTV infection and subsequent mammary tumorigenesis differs drastically, from absolute resistance to high susceptibility. For example, mice of the C3H/HeN or BALB/cJ strains are highly susceptible, whereas mice of the I/LnJ strain are highly resistant. We found that IJLnJ mice neonatally infected with MMTV produced avirulent virus particles, as they were coated with anti-virus antibodies of IgG2a isotype. The same antibodies were found in the sera of infected IJLnJ mice and were capable of neutralizing MMTV infection. The antibodies were reactive against env and gag gene products. Imrnunoglobulin isotope distribution was found to be normal in sera of uninfected I/LnJ mice, and immunization with virion proteins did not cause a bias production of anti-virus antibodies towards IgG2a isotype. Furthermore, JILnJ mice infected with another retrovirus, murine leukemia virus, also produced anti-virus neutralizing antibodies of IgG2a isotype specific for Env. Thus, it appears that the production of anti-virus antibodies of IgG2 isotype is a specialized response to retrovirus infection in I/LnJ mice. We established that a single gene (virus infectivity controller or vic) determines the production of these neutralizing antibodies in MMTV-infected JILnJ mice. The vic' about (resistant) allele found in JJLnJ mice is recessive to the vicS (susceptible) allele in C3WHeN or BALB/cJ mice. We plan to investigate the molecular mechanism of anti-virus antibody production and clone the gene conferring the resistant phenotype in I/LnJ mice.

描述（由申请方提供）：小鼠乳腺肿瘤病毒（MIMTV）是一种 外源性乳传播逆转录病毒，在一些人中诱导乳腺肿瘤 实验室小鼠的品系。MMTV从哺乳期幼崽的肠道携带到 通过淋巴细胞进入乳腺。对外源性MMTV感染的易感性 和随后的乳腺肿瘤发生有很大的不同，从绝对 抗高敏感性。例如，C3 H/HeN或BALB/cJ小鼠 品系是高度敏感的，而I/LnJ品系的小鼠是高度敏感的。 抵抗我们发现，经腹腔感染MMTV的IJLnJ小鼠产生了 无毒病毒颗粒，因为它们被抗病毒抗体包被， IgG 2a同种型。在感染IJLnJ的血清中也发现了相同的抗体 小鼠，并能够中和MMTV感染。将抗体 对env和gag基因产物具有反应性。免疫球蛋白同位素 在未感染的I/LnJ小鼠的血清中发现分布正常， 用病毒体蛋白免疫不会引起抗病毒的偏倚产生 抗IgG 2a同种型抗体。此外，JILnJ小鼠感染了另一种 逆转录病毒，小鼠白血病病毒，也产生抗病毒中和 特异于Env.因此，看来， IgG 2同种型抗病毒抗体的产生是一种特异性反应 I/LnJ小鼠中逆转录病毒感染。我们确定了单个基因（病毒） 感染性控制器或维克）决定这些中和的 MMTV感染的JILnJ小鼠中的抗体。维克者的等位基因 在JJLnJ小鼠中，对于C3 WHeN中的vicS（易感）等位基因是隐性的，或 BALB/cJ小鼠。我们计划研究抗病毒的分子机制 抗体生产和克隆赋予抗性表型的基因， I/LnJ小鼠。