THE ROLE OF MURINE AIM1 IN NEURAL CREST/MELANOCYTE DEVELOPMENT

小鼠 AIM1 在神经嵴/黑素细胞发育中的作用

• 批准号: 6108990
• 负责人: William J Pavan
• 金额: --
• 依托单位: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6108990
• 关键词: biological models; cell cycle; developmental genetics; developmental neurobiology; gene expression; in situ hybridization; laboratory mouse; melanocyte; melanoma; model design /development; neoplastic transformation; neural plate /tube; northern blottings; polymerase chain reaction; restriction fragment length polymorphism

AIM1 was identified in a substractive hybridization experiment that selected for cDNAs that are absent in melanoma (AIM). AIM1 is not expressed in a human tumorigenic melanoma cell line (UACC- 903) yet highly expressed in a non-tumorogenic melanoma cell line suppressed by introduction of human chromosome 6 (MCH- 361C1). We are developing a mouse model system to study the role of AIM1 in melanoma biology and normal melanocyte development. The mouse homologue of AIM1, muAIM1, was isolated from an adult liver cDNA library using the GeneTrapper (LTI) method. Comparison of the nucleic acid sequences and deduced open reading frame demonstrated over 85% identity in restricted areas of the gene. Sequence database searches identified regions of AIM1 with similarity to beta, gamma-crystallin family, flanked by regions of AIM1 with no obvious similarity to other proteins. The location of muAIM1 in the mouse genome was examined by PCR- RFLP using the Jackson laboratory backcross panel and found to reside on proximal mouse chromsome 10; a region syntenic to human chromsome 6. To further investigate the role of AIM1 in melanocyte development and malignant transformation, RT-PCR, Northern blot and in situ hybridization analyses were used to determine the expression pattern of muAIM1 in adult mouse tissues and during embryonic development. Correlation with the developing hair follicle was the most striking developmental feature.

AIM1在消减杂交中被鉴定 为黑色素瘤中缺失的cDNA选择的实验 (目标)。AIM1在人类致瘤性黑色素瘤中不表达 细胞系(UACC-903)在非致瘤细胞中高表达 人基因导入对黑色素瘤细胞株的抑制作用 6号染色体(MCH-361C1)。我们正在开发一种老鼠模型 研究AIM1在黑色素瘤生物学和正常中的作用的系统 黑素细胞发育。AIM1的小鼠同源物， MuAIM1是从一个成人肝脏的c DNA文库中利用 GeneTrapper(LTI)法。两种核酸的比较 序列和推导出的开放阅读框架显示85%以上 在基因的限制性区域中的身份。序列数据库搜索 确定AIM1与β、γ-晶体蛋白相似的区域 AIM1家族，侧翼为AIM1区域，与 其他蛋白质。MuAIM1在小鼠基因组中的位置是 用杰克逊实验室回交进行的PCR-RFLP检测 并发现位于近端的小鼠染色体10上； 与人类染色体6的区域共线。为了进一步研究 AIM1在黑素细胞发育和恶性中的作用 转化、RT-PCR、Northern印迹和原位杂交 通过分析确定muAIM1的表达模式 在成年小鼠组织和胚胎发育期间。 与毛囊发育的相关性最为显著。 发育特点。