| Title: |
Overexpression of Igf2-derived Mir483 inhibits Igf1 expression and leads to developmental growth restriction and metabolic dysfunction in mice |
| Authors: |
Ionel Sandovici; Denise S. Fernandez-Twinn; Niamh Campbell; Wendy N. Cooper; Yoichi Sekita; Ilona Zvetkova; David Ferland-McCollough; Haydn M. Prosser; Lila M. Oyama; Lucas C. Pantaleão; Danilo Cimadomo; Karina Barbosa de Queiroz; Cecilia S.K. Cheuk; Nicola M. Smith; Richard G. Kay; Robin Antrobus; Katharina Hoelle; Marcella K.L. Ma; Noel H. Smith; Stefan H. Geyer; Lukas F. Reissig; Wolfgang J. Weninger; Kenneth Siddle; Anne E. Willis; Brian Y.H. Lam; Martin Bushell; Susan E. Ozanne; Miguel Constância |
| Source: |
Cell Reports, Vol 43, Iss 9, Pp 114750- (2024) |
| Publisher Information: |
Elsevier, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Biology (General) |
| Subject Terms: |
CP: Developmental biology; Biology (General); QH301-705.5 |
| Description: |
Summary: Mir483 is a conserved and highly expressed microRNA in placental mammals, embedded within the Igf2 gene. Its expression is dysregulated in a number of human diseases, including metabolic disorders and certain cancers. Here, we investigate the developmental regulation and function of Mir483 in vivo. We find that Mir483 expression is dependent on Igf2 transcription and the regulation of the Igf2/H19 imprinting control region. Transgenic Mir483 overexpression in utero causes fetal, but not placental, growth restriction through insulin-like growth factor 1 (IGF1) and IGF2 and also causes cardiovascular defects leading to fetal death. Overexpression of Mir483 post-natally results in growth stunting through IGF1 repression, increased hepatic lipid production, and excessive adiposity. IGF1 infusion rescues the post-natal growth restriction. Our findings provide insights into the function of Mir483 as a growth suppressor and metabolic regulator and suggest that it evolved within the INS-IGF2-H19 transcriptional region to limit excessive tissue growth through repression of IGF signaling. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2211-1247 |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S221112472401101X; https://doaj.org/toc/2211-1247 |
| DOI: |
10.1016/j.celrep.2024.114750 |
| Access URL: |
https://doaj.org/article/abbc32c9c19d41bf953422abe96dc435 |
| Accession Number: |
edsdoj.bbc32c9c19d41bf953422abe96dc435 |
| Database: |
Directory of Open Access Journals |