Mir483-KO 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, likely through its impact on the insulin-like growth factor (IGF) signaling pathway [1]. Its dysregulation is associated with a number of human diseases such as metabolic disorders, certain cancers, and potentially autism spectrum disorder [1,3,4]. Animal models, especially mouse models, have been crucial for understanding its function.

In mouse models, transgenic overexpression of Mir483 in utero leads to fetal growth restriction via 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, indicating Mir483 functions as a growth suppressor and metabolic regulator [1]. In C2C12 myoblast cells, CRISPR/Cas9-mediated knockout of miR483 leads to down-regulation of Igf2 expression and a reduced proliferation rate, suggesting a positive feedback between miR483 and Igf2 promoter activity [2].

In conclusion, Mir483 plays essential roles in growth and metabolic regulation, as revealed by model-based research. Mouse models, especially those with Mir483 overexpression or knockout, have provided valuable insights into its functions in growth restriction and metabolic dysfunction, as well as its potential role in cancer and other diseases. Understanding Mir483 can potentially offer new strategies for treating related disorders.

References:

1. Sandovici, Ionel, Fernandez-Twinn, Denise S, Campbell, Niamh, Ozanne, Susan E, Constância, Miguel. 2024. Overexpression of Igf2-derived Mir483 inhibits Igf1 expression and leads to developmental growth restriction and metabolic dysfunction in mice. In Cell reports, 43, 114750. doi:10.1016/j.celrep.2024.114750. https://pubmed.ncbi.nlm.nih.gov/39283743/

2. Naboulsi, Rakan, Larsson, Mårten, Andersson, Leif, Younis, Shady. 2021. ZBED6 regulates Igf2 expression partially through its regulation of miR483 expression. In Scientific reports, 11, 19484. doi:10.1038/s41598-021-98777-0. https://pubmed.ncbi.nlm.nih.gov/34593874/

3. Li, Xingnan, Nadauld, Lincoln, Ootani, Akifumi, Ji, Hanlee P, Kuo, Calvin J. 2014. Oncogenic transformation of diverse gastrointestinal tissues in primary organoid culture. In Nature medicine, 20, 769-77. doi:10.1038/nm.3585. https://pubmed.ncbi.nlm.nih.gov/24859528/

4. Qiu, Shuang, Qiu, Yingjia, Li, Yong, Cheng, Yi, Liu, Yawen. 2023. Nexus between genome-wide copy number variations and autism spectrum disorder in Northeast Han Chinese population. In BMC psychiatry, 23, 96. doi:10.1186/s12888-023-04565-7. https://pubmed.ncbi.nlm.nih.gov/36750796/