Mir483-flox Mouse

Mir483 is a conserved and highly expressed microRNA in placental mammals, embedded within the Igf2 gene. It is involved in regulating growth and metabolism, potentially through its effects on the insulin-like growth factor (IGF) signaling pathway. Dysregulation of Mir483 expression is associated with various human diseases such as metabolic disorders and certain cancers [1].

In mice, transgenic overexpression of Mir483 in utero leads to fetal growth restriction through the repression of Igf1 and Igf2, and also causes cardiovascular defects resulting in fetal death. Post-natal overexpression leads to growth stunting, increased hepatic lipid production, and excessive adiposity, which can be rescued by IGF1 infusion [1]. Disruption of the ZBED6-Igf2 interaction in transgenic mice causes a significant up-regulation of miR483 expression. CRISPR/Cas9-mediated knockout of miR483 in C2C12 myoblast cells leads to down-regulation of Igf2 expression and a reduced proliferation rate [2].

In conclusion, Mir483 functions as a growth suppressor and metabolic regulator, likely evolving within the INS-IGF2-H19 transcriptional region to limit excessive tissue growth via IGF signaling repression. Mouse models, especially those with Mir483 overexpression or knockout, have been crucial in revealing its role in growth and metabolic diseases, as well as its complex regulatory relationship with Igf2 [1,2].