Screening And Cloning The Genes Related To Heterogeneity Of Traumatic Responses In The Interstrain Mice

The individual susceptibility to the same kind and degree of trauma varies each other, many researches indicated that the individual genetic background may be one of the most important factors, but which gene or genes control it remains unclear. Considering that multiple organs and tissues are involved in the systemic response to trauma, we suggest that it should be controlled by multigenes which is also supported by other correlative studies. The pathogenesis determined by multigenes is one of the difficult and complicated problems in the field of medical molecular genetics all the while. However, with the rapid development of theories and technology in molecular biology and molecular genetics and great progress made in human and other organisms (model systems) genome project in last two decades, many strategies and methods such as cDNA microarray (gene chips) and suppression subtractive hybridization (SSH) were developed to screen and clone the genes associated with these complicated traits.In this study, we chose BALB/C and C57BL/6 inbred mice as research object and developed a systemic blast injury animal model. The experiments were divided into four parts as follows: (1) Comparison of the early traumatic response between BALB/C and C57BL/6 inbred mice exposed to the same degree of systemic blast injury. (2) Comparison of the differential expressed genes in lung and liver tissues in the early stage of systemic blast injury between these two mice strains with cDNA microarray. (3) Screening the differential expressed genes in brain tissue in the initial stage(l hour after injury) of the systemic blast injury in BALB/C mice with suppressionsubtractive hybridization, and comparing of the expression profile of these genes between BALB/C and C57BL/6 brain. (4) Observing the protein production and gene expression of interferon-gamma in the serum and lung tissues which is definitely related to the traumatic pathological process between the two strains in the early stage of the systemic blast injury.The purpose of this study is to observe whether there is interstrain variation of traumatic susceptibility between BALB/C and C57BL/6 inbred mice, and investigate the possible molecular genetic mechanisms involved in this phenotype trait.The main results and conclusions of the experiments are as follows:1. A stable systemic blast injury model of mice was developed, which can be used to compare the susceptibility to traumatic response of mice, the animal doesn't need to be anesthetized and up to 60 mice can be injured in one experiment.2. The results of animal experiments indicated that there were significant differences in the mortality and the severity of lung injury between C57BL/6 and BALB/C inbred mice within 72 hours after blast injury. The C57BL/6 showed greater ability of resistance to the blast injury, and suffered from milder lung injuries than those of BALB/C mice.3. Furthermore, the death of the mice almost occurred within 6 hours after blast injury, but no significant differences in mortality and the severity of lung injury were seen between the male and the female mice of both strains.4. The cluster analyses of cDNA microarray data indicated there are differences in the genome expression of liver tissues between BALB/C and C57BL/6 mice in the early stage of systemic blast injury, the differential expressed genes are mainly involved in stress, inflammation, tissue injury and repair, cell signal pathway, biological oxidation and materialmetabolism and so on. The C57BL/6's stronger stress ability than that of BABL/C may be associated with its more resistant to blast injury.5. The cluster analyses of cDNA microarray data also indicated a lot of genes related to tissues damage, antiperoxidation process, inflammation, apoptosis and cell signal pathway differentially expressed in the lung tissues of BALB/C and C57BL/6 mice in the early stage of systemic blast injury. The up-regulated genes related to tissues damage to the lung...