Asb2-KO Mouse

Asb2, short for ankyrin repeat and SOCS Box containing 2, is a gene encoding a protein that functions as a key subunit of a Cullin5 Ub ligase complex [3]. It is involved in the ubiquitin-proteasome system, which is crucial for the selective degradation of proteins. Asb2 is associated with pathways such as BMP signalling, NF-κB pathway, and is important in processes like cardiogenesis, hematopoietic cell differentiation, and NK cell migration [1,2,4]. Genetic models, especially KO/CKO mouse models, have been instrumental in studying its functions.

In KO mouse models, deletion of Asb2 leads to embryonic lethality, heart defects like double outlet right ventricle (DORV), and placental defects [3,6]. In zebrafish, knockdown of Asb2 results in a thinned ventricular wall and dilated ventricle, which can be rescued by simultaneous knockdown of Smad9, indicating its role in cardiogenesis through regulation of BMP signalling [1]. In GCB DLBCL cell lines, down-regulation of Asb2 is toxic and induces NF-κB inhibition, suggesting its importance in sustaining NF-κB pathway activation in this type of lymphoma [2]. In NK cells, knockdown of ASB2 inhibits migration, showing its role in regulating NK cell migration [4]. In leukemia cells, knockdown of endogenous ASB2 delays retinoic acid-induced differentiation and filamin degradation [5].

In conclusion, Asb2 plays essential roles in multiple biological processes, particularly in cardiogenesis, cell differentiation, and immune cell function. The use of KO/CKO mouse models has significantly contributed to understanding its functions in heart development-related diseases like DORV and in cancer-related processes such as lymphoma development and leukemia cell differentiation [1,2,3,5,6].

References:

1. Min, Kyung-Duk, Asakura, Masanori, Shirai, Manabu, Takashima, Seiji, Kitakaze, Masafumi. 2021. ASB2 is a novel E3 ligase of SMAD9 required for cardiogenesis. In Scientific reports, 11, 23056. doi:10.1038/s41598-021-02390-0. https://pubmed.ncbi.nlm.nih.gov/34845242/

2. Sartori, Giulio, Napoli, Sara, Cascione, Luciano, Thome, Margot, Bertoni, Francesco. 2021. ASB2 is a direct target of FLI1 that sustains NF-κB pathway activation in germinal center-derived diffuse large B-cell lymphoma. In Journal of experimental & clinical cancer research : CR, 40, 357. doi:10.1186/s13046-021-02159-3. https://pubmed.ncbi.nlm.nih.gov/34763718/

3. Yamak, Abir, Hu, Dongjian, Mittal, Nikhil, Ellinor, Patrick T, Domian, Ibrahim J. 2020. Loss of Asb2 Impairs Cardiomyocyte Differentiation and Leads to Congenital Double Outlet Right Ventricle. In iScience, 23, 100959. doi:10.1016/j.isci.2020.100959. https://pubmed.ncbi.nlm.nih.gov/32179481/

4. Shin, June Ho, Moreno-Nieves, Uriel Y, Zhang, Luhua H, Mace, Emily M, Sunwoo, John B. 2021. AHR Regulates NK Cell Migration via ASB2-Mediated Ubiquitination of Filamin A. In Frontiers in immunology, 12, 624284. doi:10.3389/fimmu.2021.624284. https://pubmed.ncbi.nlm.nih.gov/33717133/

5. Heuzé, Mélina L, Lamsoul, Isabelle, Baldassarre, Massimiliano, Calderwood, David A, Lutz, Pierre G. 2008. ASB2 targets filamins A and B to proteasomal degradation. In Blood, 112, 5130-40. doi:10.1182/blood-2007-12-128744. https://pubmed.ncbi.nlm.nih.gov/18799729/

6. Park, Seul Gi, Kim, Eun-Kyoung, Nam, Ki-Hoan, Lee, Beom Jun, Nam, Sang-Yoon. 2021. Heart defects and embryonic lethality in Asb2 knock out mice correlate with placental defects. In Cells & development, 165, 203663. doi:10.1016/j.cdev.2021.203663. https://pubmed.ncbi.nlm.nih.gov/33993984/