Eif4ebp2-KO Mouse

Eif4ebp2, encoding the eukaryotic initiation factor 4E (eIF4E)-binding protein 2 (4E-BP2), is a suppressor of mRNA translation initiation. It sequesters eIF4E, thereby blocking cell growth and proliferation, and is involved in pathways related to protein synthesis regulation. Genetic models have been crucial for studying its functions [3].

In Eif4ebp2 knockout (Eif4ebp2(-/-)) mice, there is an imbalance in excitatory-to-inhibitory neurotransmission and autistic-like behaviors such as deficits in social interaction and repetitive behaviors. These phenotypes can be reversed by antagonists of group I metabotropic glutamate receptors (mGluRs), indicating Eif4ebp2's role in regulating synaptic physiology and behaviors related to autism spectrum disorders (ASDs) [2]. miR-23 directly targets the mRNA of Eif4ebp2, and this regulation contributes to the control of proliferation of lipid-associated macrophages, which is related to protection against diet-induced obesity metabolic dysfunction [1].

In conclusion, Eif4ebp2 is an important regulator of mRNA translation initiation. Its deficiency in mouse models reveals its role in synaptic function, ASD-like behaviors, and macrophage proliferation. These findings contribute to understanding the mechanisms underlying ASDs and metabolic diseases, highlighting the significance of Eif4ebp2 in these biological processes and disease conditions.

References:

1. Sprenkle, Neil T, Winn, Nathan C, Bunn, Kaitlyn E, Hasty, Alyssa H, Pua, Heather H. 2023. The miR-23-27-24 clusters drive lipid-associated macrophage proliferation in obese adipose tissue. In Cell reports, 42, 112928. doi:10.1016/j.celrep.2023.112928. https://pubmed.ncbi.nlm.nih.gov/37542720/

2. Aguilar-Valles, Argel, Matta-Camacho, Edna, Khoutorsky, Arkady, Lacaille, Jean-Claude, Sonenberg, Nahum. . Inhibition of Group I Metabotropic Glutamate Receptors Reverses Autistic-Like Phenotypes Caused by Deficiency of the Translation Repressor eIF4E Binding Protein 2. In The Journal of neuroscience : the official journal of the Society for Neuroscience, 35, 11125-32. doi:10.1523/JNEUROSCI.4615-14.2015. https://pubmed.ncbi.nlm.nih.gov/26245973/

3. Martineau, Y, Azar, R, Bousquet, C, Pyronnet, S. 2012. Anti-oncogenic potential of the eIF4E-binding proteins. In Oncogene, 32, 671-7. doi:10.1038/onc.2012.116. https://pubmed.ncbi.nlm.nih.gov/22508483/