The functional genomics is coming of age after the anatomy of the human genome is completed .The dramatic increase in the amount of genomic information is having a tremendous impact on biomedical research and on the w...The functional genomics is coming of age after the anatomy of the human genome is completed .The dramatic increase in the amount of genomic information is having a tremendous impact on biomedical research and on the way that medical treatment is processed,the major task is how to dissert the function of genes using large_scale and systematic approaches.Since genes function in the complex living creatures made of cells ,the study of functional genomics will largely rely on the research of model organisms.The mouse is the closest mammalian model organism to human.Compared with other organism,mouse has many advantanges,short lifecycle,close genome size (2 5 ×10 9 bp in mouse vs 2 9 ×10 9 bp in human),available whole genome sequences and many inbred strains, easy to breed and maitain in lab. The most importantly, the genetic information of mouse gene could be modified in vivo by transgenic and gene targeting approaches. The mouse science is changing the modern biology study in general. The invention of gene targeting is an important landmark since the generation of the first transgenic mouse 22 years ago. Gene targeting is an approach to alter the genomic information in vivo based on the embryonic stem cell technology and the homologous recombination. It has become one of the most straight forward and powerful approaches for studying gene function in the post_genome era. The gene targeting techniques have been improves in three different ways:1) Gene targeting with spatial and temporal control;2)Large scale of random gene knockout;3)Introduction of subtle mutations .The first generation of mouse models is being replaced by the second generation of mouse models based on the conditional gene targeting approaches. The second generation of mouse models based on the Cre_LoxP system that can mimic the somatic mutation related to human diseases provides exciting new chance to study the mechanisms of genes during the initiation, progress and treatment of human disease. Researches in gene targeting field supported by National Natural Science Foundation of China and the National High_Tech Research and Development have been initiated. The base laboratories for generating mouse models for human diseases with transgenic and gene targeting as plat techniques have been established respectively in Shanghai and Beijing. The establishment of national resource bank for genetic engineered mice in Nanjing supported by Ministry of Science and Technology will boost researches in this field . Our laboratory has focused on studying the function of genes related to the developmental processes and diseases and generating mouse models for human diseases using transgenic and gene targeting approaches in recent years. We had generated HbsAg and HBx gene knock in transgenic mice that developed well differentiated hepatocellular carcinoma respectively at ages of older than 1 year. These mice will help us to study the early events and mechanisms of HBV related hepatocarcinogenesis. To further study the function of SMADs,intracellular transducers of TGF_ β ,in mammalian organgenesis and related diseases, Smads conditional gene targeting mice and series of tissue specific Cre transgenic mice were generated.Multiple tissue specific Smad4 knockout mice were generated by breeding the Smad4 conditional gene targeting mouse with the tissue specific Cre transgenic mice .Tissue specific inactivation of Smad4 gene in different tissues gave rise to viable animals with obvious phenotypes related to diseases.The successful creation of viable tissues specific Smad4 knockout mouse models will benefit the detailed analysis of the function of Smad4 in development and related diseases.展开更多
文摘The functional genomics is coming of age after the anatomy of the human genome is completed .The dramatic increase in the amount of genomic information is having a tremendous impact on biomedical research and on the way that medical treatment is processed,the major task is how to dissert the function of genes using large_scale and systematic approaches.Since genes function in the complex living creatures made of cells ,the study of functional genomics will largely rely on the research of model organisms.The mouse is the closest mammalian model organism to human.Compared with other organism,mouse has many advantanges,short lifecycle,close genome size (2 5 ×10 9 bp in mouse vs 2 9 ×10 9 bp in human),available whole genome sequences and many inbred strains, easy to breed and maitain in lab. The most importantly, the genetic information of mouse gene could be modified in vivo by transgenic and gene targeting approaches. The mouse science is changing the modern biology study in general. The invention of gene targeting is an important landmark since the generation of the first transgenic mouse 22 years ago. Gene targeting is an approach to alter the genomic information in vivo based on the embryonic stem cell technology and the homologous recombination. It has become one of the most straight forward and powerful approaches for studying gene function in the post_genome era. The gene targeting techniques have been improves in three different ways:1) Gene targeting with spatial and temporal control;2)Large scale of random gene knockout;3)Introduction of subtle mutations .The first generation of mouse models is being replaced by the second generation of mouse models based on the conditional gene targeting approaches. The second generation of mouse models based on the Cre_LoxP system that can mimic the somatic mutation related to human diseases provides exciting new chance to study the mechanisms of genes during the initiation, progress and treatment of human disease. Researches in gene targeting field supported by National Natural Science Foundation of China and the National High_Tech Research and Development have been initiated. The base laboratories for generating mouse models for human diseases with transgenic and gene targeting as plat techniques have been established respectively in Shanghai and Beijing. The establishment of national resource bank for genetic engineered mice in Nanjing supported by Ministry of Science and Technology will boost researches in this field . Our laboratory has focused on studying the function of genes related to the developmental processes and diseases and generating mouse models for human diseases using transgenic and gene targeting approaches in recent years. We had generated HbsAg and HBx gene knock in transgenic mice that developed well differentiated hepatocellular carcinoma respectively at ages of older than 1 year. These mice will help us to study the early events and mechanisms of HBV related hepatocarcinogenesis. To further study the function of SMADs,intracellular transducers of TGF_ β ,in mammalian organgenesis and related diseases, Smads conditional gene targeting mice and series of tissue specific Cre transgenic mice were generated.Multiple tissue specific Smad4 knockout mice were generated by breeding the Smad4 conditional gene targeting mouse with the tissue specific Cre transgenic mice .Tissue specific inactivation of Smad4 gene in different tissues gave rise to viable animals with obvious phenotypes related to diseases.The successful creation of viable tissues specific Smad4 knockout mouse models will benefit the detailed analysis of the function of Smad4 in development and related diseases.
