Study On The Behavioer Of Mice With Astrocyte-specific Knockout Of KLF7 Gene

Krüppel-like factors(KLFs)are zinc finger transcription factors,which are involved in the regulation of cell proliferation,differentiation,apoptosis and other life processes.KLF7 is a member of Krüppel like factor,which is involved in the development of sensory neurons and sympathetic neurons,and can promote the growth of neuronal axons,playing an important role in the nervous system.Studies have shown that related phenotypes of autism are associated with insufficient haploid dose of KLF7,while the pathogenesis of some neurological diseases,including epilepsy and ID/DD(mental retardation/retardation),has also been shown to be associated with copy number variation(CNV)of genes,of which KLF7 is one of the related genes.Currently,whole-body KLF7 knockout mouse models have been used to study the role of KLF7 in various diseases.However,homozygous mice without KLF7 have a mortality rate of 97 % within 2d after birth,making it difficult to obtain mature homozygous individuals.In this study,KLF7 was specifically knocked out in astrocytes,and the homozygous survival rate was very high,so we obtained a large number of mature astrocytes with homozygous individuals lacking KLF7.We found that after reaching the age of 6 months,they showed obvious epileptic behavior,and the disease became more serious with the increase of age.Through the behavior experiments of three-chamber social interaction,Y maze,elevated cross maze and so on,we found that the abnormal behavior of the mice was also manifested in the decline of their social tendency and some degree of hyperactivity.At the same time,their emotions also appear abnormal,specifically manifested in the normal anxiety and fear of weakening.Abnormal astrocyte function is closely related to the occurrence of neurological diseases.Studies have found that astrocytes often change in cell number,morphology and biochemical indexes during the course of epilepsy.We found that the differences of the gene is mainly enriched in calcium signaling pathways,Benzedrine addiction pathway and glutamate synaptic pathways,to test the key genes of these pathways,we found that the ionic glutamate receptors and metabolic type high glutamate receptors are expressed,further determine the knockout mice have epilepsy,the rise of voltage dependent calcium channel protein expression and on the other hand,confirms this view.In addition,we found a change in the expression of tyrosine hydroxylase in knockout mice,suggesting that the abnormal behavior of our mice may be the result of a combination of many diseases,which also makes us more inclined to classify epilepsy as a manifestation of ASD.