TRANSGENIC ANIMAL MODELS USING YACS

使用 YACS 的转基因动物模型

• 批准号: 3506204
• 负责人: Ted Choi
• 金额: $ 20.07万
• 依托单位: GENPHARM INTERNATIONAL, INC.
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-05-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3506204
• 关键词: artificial chromosomes; biological models; gene rearrangement; genetically modified animals; human genetic material tag; hybridomas; immunoglobulin genes; laboratory mouse; method development; molecular cloning; monoclonal antibody; transfection

The goal of GenPharm's program is to develop methods for the introduction of yeast artificial chromosomes (YACs) into the germline of mice, and to apply the technology toward the generation of transgenic mice expressing a broad, fully human immunoglobulin repertoire. These mice would permit the isolation of human monoclonal antibodies in an analogous manner to rodent monoclonal antibodies. In Phase I, methods for the introduction of YACs into mice were developed, and mice carrying a small YAC encoding a minimally competent human immunoglobulin transgene were shown to express human heavy chain IgM antibodies in the serum. In Phase II, the animals generated in Phase I will be fully characterized for transgene function and expression. Additional constant and variable regions will be cloned in YACs and added to the Phase I YAC to permit class switching, somatic mutation, and IgGproduction. These Phase II transgenes will be introduced into mice using methodology developed in Phase I. Transgenic mice will also be generated carrying large fragments of the unrearranged human kappa gene and bred to the Phase II heavy chain mice. These mice will be bred with mice lacking functional immunoglobulin genes to produce mice demonstrating a broad repertoire of high affinity, fully human antibodies.

GenPharm项目的目标是开发引进的方法