Functional Analysis Of Mouse Mir-200Family In Regulating The Body Size And Adipogenesis

The expression and function of microRNA-200family in epithelial tumors is a hot topic of research at present, while little studies are focused on the mechanisms of miR-200family in body size control. In2009, researchers found that miR-8plays important roles in regulating the body size of fly, miR-8null flies becomes very small than controls. As the homologue gene of miR-8in mammals, whether miR-200family has similar function and how it performs its function needs our further studies. The purpose of this study was to elucide the roles of miR-200family in body size control.miR-200family contains five members, they are miR-200a,miR-200b,miR-200c, miR-141and miR-429, which are classified into two clusters: miR-200b/miR-200a/miR-429cluster and miR-200c/miR-141cluster depends upon their location in the chromosome. In this study, we generated mice in which the miR-200b/miR-200a/miR-429cluster was floxed with two loxp sequences using the Cre-loxp system. The adipose-specific miR-200b/200a/429cluster knockout mice were obtained by crossing the FABP4-Cre transgenic mice and loxp-floxed mice. Phenotypic characters such as growth curve, metabolism conditions, serum biochemical and histological sections were examined, the results indicated that the deletion of miR-200b/200a/429cluster did not result in embryonic lethality; the conditional knockout mice(CKO) began to grow slower at4-week-old, at the end of12-weeks, the mouse is sacrificed and its fat mass was50%less than control mice; the CKO mice was glucose tolerant and insulin resistant, and the serum IGF1was reduced while the serum Adiponectin were raised significantly. Histological analysis showed there are no significant changes in fat and muscle tissues, while the liver necrosis was aggravated in CKO mice. Through target gene prediction and interaction analysis, we found that the inhibition of PI3K-Akt-mTOR pathway maybe one of the main causes of weight less and fat loss in miR-200b/200a/429cluster knockout mice. In conclusion, our study provided the first genetic evidence to show that miR-200family was essential in body size control and adipogenesis. We proposed that miR-200family may activate the PI3K-Akt-mToR signaling to inhibit the adipogenesis process. The adipose-specific miR-200b/200a/429cluster knockout mice could serve as a useful animal model for further investigating the mechanisms of adipocyte differentiation, and the new mechanisms of miR-200family interacted with PI3K-Akt-mToR signaling will provide theoretical references for the functional studies of miR-200family in regulating the development of animals.