MUTANTS FOR CELL ADHESION MOLECULES

描述(改编自调查员的具体目标)：总体情况 这个项目的目标是使用遗传策略来研究 白细胞和内皮细胞黏附分子在正常生物学和 疾病过程。提出了五个具体目标： (1)所有三种小鼠选择素基因都发生突变。 (2)对基因敲除小鼠进行表型鉴定，包括常规 病理、白细胞计数、腹膜炎、肺炎、延迟型 过敏反应和活体显微镜检查。 (3)探讨CD18在银屑病样皮肤病发病机制中的作用 缺陷小鼠，特别是使用一个或多个修饰性基因 全基因组连锁策略。 (4)利用loxP/Cre开发细胞特异性和诱导性突变 重组酶系统，包括内皮细胞特异性突变 VCAM-1和ICAM-1的诱导性突变。 (5)探讨黏附分子在糖尿病发病机制中的作用。 使用载脂蛋白E缺陷小鼠的动脉粥样硬化。

DESCRIPTION (Adapted from the Investigator's Specific Aims): The overall goals of this project are to use genetic strategies to study the role of leukocyte and endothelial cell adhesion molecules in normal biology and in disease processes. Five Specific Aims are proposed: (1) Develop mutations in all three mouse selectin genes. (2) Perform phenotypic evaluation of knockout mice, including routine pathology, leukocyte counts, peritonitis, pneumonia, delayed type hypersensitivity reactions, and intravital microscopy. (3) Investigate the pathogenesis of psoriasis-like skin disease in CD18 deficient mice, specifically searching for a modifier gene or genes using a genomic-wide linkage strategy. (4) Develop cell-specific and inducible mutations using the loxP/Cre recombinase system, including an endothelial cell-specific mutation for VCAM-1 and an inducible mutations for ICAM-1. (5) Evaluate the role of adhesion molecules in the pathogenesis of atherosclerosis using apolipoprotein E-deficient mice.