DEVELOPMENT OF TRANSGENIC MICE INFECTABLE WITH HIV1

描述（改编自申请人的摘要）：本申请的目的 研究建议是开发一种小动物模型，更具体地说， HIV-1感染和AIDS的小鼠模型。 像老鼠这样的小动物 不会感染HIV-1，因为它们没有HIV-1受体， 人CD 4分子 然而，即使它们表达hCD 4，小鼠 细胞不能被HIV-1感染，因为它们缺乏合适的免疫系统。 共受体 最近对这些共受体的鉴定使小鼠 体外培养的可被HIV-1感染的细胞。 调查人员已 构建的转基因小鼠表达hCD 4和一种或两种 共受体CXCR-4和CCR-5。 他们建议（1）描述模式 CXCR-4和CCR-5在这些小鼠中的表达， 表达转基因的细胞亚群;（2）建立实验性的 体外感染来自这些Tg小鼠的原代细胞的条件;（3）产生 HIV-1变异体在来自这些Tg的细胞中复制能力增加 小鼠在体外和体内;和（4）建立条件，以获得 这些Tg小鼠的生产性和有效感染。

DESCRIPTION (adapted from applicant's abstract): The objective of this research proposal is to develop a small animal model, more specifically, a mouse model of HIV-1 infection and of AIDS. Small animals such as mice are not infectable with HIV-1 because they do not harbor the receptor for HIV-1, the human CD4 (hCD4) molecule. However, even if they express hCD4, mouse cells are not infectable by HIV-1 because they lack an appropriate co-receptor. The recent identification of these co-receptors has made mouse cells in culture infectable by HIV-1 in vitro. The investigators have constructed transgenic mice expressing both hCD4 and one or both of the co-receptors CXCR-4 and CCR-5. They propose to (1) characterize the pattern of CXCR-4 and CCR-5 expression in these mice and to identify the specific subset of cells expressing the transgenes; (2) establish experimental conditions to infect primary cells from these Tg mice in vitro; (3) generate HIV-1 variants with increased capacity to replicate in cells from these Tg mice both in vitro and in vivo; and (4) establish conditions to get productive and efficient infection of these Tg mice.