Effects Of Meg8-DMR On Growth And Development Of Skeletal Muscle In Mice

The Dlk1-Dio3 imprinted gene cluster is an extremely important imprinted gene cluster on the mouse chromosome,which is located at the end of the mouse chromosome 12 and is about 1Mb in length.The Dlk1-Dio3 imprinted gene cluster contains three Dlk1,Rtl1 and Dio3 paternally expressed coding genes,maternally expressed long non-coding RNAs,and mi RNAs and sno RNAs,which have important effects on mouse development and disease development.If the expression of the imprinted gene in this area is abnormal,it will cause disease,stunting,or death of the individual.Meg8-DMR is the first differential methylation region of maternal methylation found in the Dlk1-Dio3 imprinted gene cluster in our laboratory.Its regulatory role and function in the development of organisms are not yet known,so this Meg8-DMR knockout mice were used as models to study their effects on mouse skeletal muscle development.It is likely to have important impact.First,using the Meg8-DMR knockout mouse model constructed in this laboratory,E18.5 embryos,Meg8-DMR knockout mice at four and six weeks of age,and their weight,morphology and muscle changes.And the expression level of each imprinted gene in imprinted gene cluster was analyzed and studied.The results showed that: Meg8-DMR knockout mice showed a slight weight loss change in body weight compared to wild-type mice.Morphological analysis showed that Meg8-DMR knockout did not have a significant inhibitory effect on mouse muscle development;Meg8-Deletion of DMR affects the expression of imprinted genes in muscle tissue.Irm has an upward trend in maternal deletion and double knock type;Rtl1 and Meg8 have an upward trend in paternal deletion.AB063319 has a downregulation in paternal deletion,upregulation occurs in both maternal deletion and double knock type.Dlk1 has a downregulation change in paternal deletion and maternal deletion.In double knock type,the downregulation is more obvious.Secondly,the Meg8-DMR knockout C2C12 cell line was constructed,and its proliferation and differentiation were studied.The results showed that Meg8-DMR knockout would inhibit the proliferation and differentiation of C2C12 cells.In summary,the lack of Meg8-DMR does not have a significant inhibitory effect on the muscle development of mice,but it affects the expression of genes in the imprinting area;at the same time,it inhibits the proliferation and differentiation of C2C12 cells.The research results lay a good foundation for further clarification of Meg8-DMR on skeletal muscle development and its regulatory mechanism.