Eps8l2-KO Mouse

Eps8l2, Epidermal growth factor receptor Pathway Substrate 8 L2, is an actin-binding protein. It is part of a family of proteins that link growth factor stimulation to actin reorganization, participating in the Ras/Rac pathway [5]. Eps8l2 is important for the maintenance of actin-based structures in various biological processes, and its function is relevant in cell migration, inner ear hair cell integrity, and potentially in meat traits of chickens [1,4,6].

In cell migration, Ctdnep1 and Eps8L2 directly interact, and this interaction is crucial for nuclear positioning. They are involved in the formation and thickness of dorsal actin cables required for TAN lines engagement during nuclear movement [1]. In the inner ear, Eps8L2 null-mutant mice display a late-onset, progressive hearing loss due to the gradual deterioration of hair bundle morphology, indicating its requirement for the long-term maintenance of auditory hair bundle structure and function [4]. In Rhodesian Ridgeback dogs, an in-frame deletion in EPS8L2 is associated with early onset adult deafness [3]. In humans, a frame-shift variant in EPS8L2 causes childhood-onset autosomal recessive progressive hearing loss [2].

In conclusion, Eps8l2 plays essential roles in cell migration-related nuclear positioning and the maintenance of inner ear hair cell function. Studies using gene-knockout mouse models and animal disease models have revealed its significance in these biological processes and in hereditary hearing disorders. Understanding Eps8l2 contributes to our knowledge of normal biological functions and the underlying mechanisms of related diseases.

References:

1. Calero-Cuenca, Francisco J, Osorio, Daniel S, Carvalho-Marques, Sofia, Cadot, Bruno, Gomes, Edgar R. 2021. Ctdnep1 and Eps8L2 regulate dorsal actin cables for nuclear positioning during cell migration. In Current biology : CB, 31, 1521-1530.e8. doi:10.1016/j.cub.2021.01.007. https://pubmed.ncbi.nlm.nih.gov/33567288/

2. Dahmani, Malika, Ammar-Khodja, Fatima, Bonnet, Crystel, Mallek, Zahia, Petit, Christine. 2015. EPS8L2 is a new causal gene for childhood onset autosomal recessive progressive hearing loss. In Orphanet journal of rare diseases, 10, 96. doi:10.1186/s13023-015-0316-8. https://pubmed.ncbi.nlm.nih.gov/26282398/

3. Kawakami, Takeshi, Raghavan, Vandana, Ruhe, Alison L, Nelson, Thomas C, Boyko, Adam R. 2022. Early onset adult deafness in the Rhodesian Ridgeback dog is associated with an in-frame deletion in the EPS8L2 gene. In PloS one, 17, e0264365. doi:10.1371/journal.pone.0264365. https://pubmed.ncbi.nlm.nih.gov/35385474/

4. Furness, David N, Johnson, Stuart L, Manor, Uri, Kachar, Bechara, Marcotti, Walter. 2013. Progressive hearing loss and gradual deterioration of sensory hair bundles in the ears of mice lacking the actin-binding protein Eps8L2. In Proceedings of the National Academy of Sciences of the United States of America, 110, 13898-903. doi:10.1073/pnas.1304644110. https://pubmed.ncbi.nlm.nih.gov/23918390/

5. Offenhäuser, Nina, Borgonovo, Alessandro, Disanza, Andrea, Di Fiore, Pier Paolo, Scita, Giorgio. 2003. The eps8 family of proteins links growth factor stimulation to actin reorganization generating functional redundancy in the Ras/Rac pathway. In Molecular biology of the cell, 15, 91-8. doi:. https://pubmed.ncbi.nlm.nih.gov/14565974/

6. Tian, Shuaishuai, Tang, Wendan, Zhong, Ziqi, Tan, Zhen, Xiao, Qian. 2023. Identification of Runs of Homozygosity Islands and Functional Variants in Wenchang Chicken. In Animals : an open access journal from MDPI, 13, . doi:10.3390/ani13101645. https://pubmed.ncbi.nlm.nih.gov/37238076/