IDENTIFYING AFR2--GENE REGULATOR IN LIVER PATHOLOGY

鉴定 AFR2——肝脏病理学中的基因调节因子

• 批准号: 2010682
• 负责人: MIRIAM H FEUERMAN
• 金额: $ 15.07万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-01-01 至 1999-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2010682
• 关键词: alpha fetoprotein; artificial chromosomes; carcinogenesis; gene expression; genetic polymorphism; genetic strain; laboratory mouse; linkage mapping; liver cells; liver regeneration; tissue /cell culture; transcription factor; transfection

DESCRIPTION: The alpha-fetoprotein (AFP) gene is an onco-fetal antigen, expressed in the developing fetus and under the pathological conditions of regeneration and tumorigenesis in the adult. The level of AFP gene expression during liver regeneration in mice is regulated by a genetically unlinked autosomal locus, Afr2. Inbred C57B1/6 mice express 8 to 10 fold less AFP during liver regeneration than wild type C3H/He mice. Lower AFP expression in regenerating liver may reflect other regulatory processes, as C57B1/6 mice are less susceptible to liver carcinogenesis than are C3H/He mice. From these and other genetic studies, it appears that the Afr2 gene is polymorphic. Since Afr2 regulates AFP expression, use of these different mouse strains provides a unique opportunity to identify a gene regulating AFP expression during liver regeneration. Using information from the Mouse Genome Project, in the first series of experiments, the Afr2 gene will be genetically mapped. Cloned DNA of this locus will be identified from a Yeast Artificial Chromosome library. Transcribed sequences will be isolated by exon-trapping and/or direction selection of cDNAs. Two criteria will be used to determine the likelihood that the transcribed sequences, as well as genes previously mapped to the locus, are Afr2: genetic linkage to the Afr2 gene and expression during liver regeneration. In the second series of experiments, a full length Afr2 cDNA clone will be prepared, transfected into a primary hepatocyte culture system, and tested for its ability to regulate AFP gene expression. Analysis of the activity of the two known Afr2 alleles will be compared. Identifying and isolating a clone of the Afr2 gene will provide a tool to study the relationships between developmental growth, controlled growth, and uncontrolled tumorigenic growth in the liver.

甲胎蛋白（AFP）基因是一种癌胎抗原，