The Establishment Of The UL122 Genetically Modified Mice Model And The Effects Of Its Coding Protein IE2 On The Nervous System

Human cytomegalovirus(HCMV)is a double stranded DNA virus that belongs to the family Herpesviridae and subfamily Beta herpesvirinae.CX43 belongs to the family members of the gap link protein family.The experimental data indicate that HCMV can lower the expression level of CX43.As glutamate receptors and ion channel proteins found in nerve cells,NMDARS has a close relationship with the learning and memory ability.IE2 is encoded by the viral gene UL122,which plays an important role in virus replication and the pathogenesis of many diseases.Previous studies have shown that in pregnant women,primary or new HCMV infection can cause intrauterine infection or perinatal infection,leading to fetal malformation,mental retardation,or developmental delay.HCMV infection in pregnancy is reported to be closely associated with neonatal delayed nerve injury.Congenital HCMV infection lead to learning and memory impairment,but whether HCMV IE2 has played a key role in this process is not clear.Due to species specificity,previous studies on HCMV IE2 were limited to cell and molecular level.In order to further study whether HCMV IE2 can influence the learning and memory ability of mice by affecting the NMDA receptor and CX43 expression level of the hippocampus neurons in UL122 genetically modified mice at the overall level.Firstly,the ul122 genetically modified mice models that can steadily and continuously express IE2 protein were established.Then,the mice were divided into the experimental group(positive mice identified)and the control group(wild type mice.n = 24 in each group).The establishment of ul122 genetically modified mice was identified by PCR technology.The learning and memory ability were measured using the Morris water-maze test.Western blot and immunohistochemical study were performed to detect the expression level of Cx43 and NMDA receptors.The results of PCR indicated that the ul122 genetically modified model was successfully constructed.Morris water maze test result showed that in the experimental group,less platform crossings and Quadrant time(%)compared to the control group,but there was no difference in escape latency.The expression level of Cx43 in the hippocampus CA1 of the experimental group was significantly reduced in keeping with NMDA receptors inimmunohistochemistryThesignificant decreased expression level of Cx43 and NMDA receptors in the ul122 genetically modified mice hippocampus may be connection with the mechanism for the spatial memory impairment In this experiment,ul122 genetically modified mice models successfully overcame the limitation of HCMV species specificity,and the effects of IE2 on the nervous system were first studied in mice.This will explainthe theoretical basis for the molecular mechanism of HCMV IE2 leading to neurodevelopmental abnormalities.