Zeb2-KO Mouse

The transcription factor ZEB2 drives the formation of age-associated B cells. In Science (New York, N.Y.), 383, 413-421. [3] In T-cells, identification of the t(2; 14)(q22; q32) translocation involving the ZEB2 locus in T-cell acute lymphoblastic leukemia suggested its role as an oncogenic driver. Loss-and gain-of-function studies in mice revealed important roles of Zeb2 during different stages of hematopoiesis, including the T-cell lineage. [2] In autoimmunity, a distinct CXCR3midCD4+ effector memory T cell subset (THA cells) that expands with age and exhibits B-cell helper functions was identified, and these features were regulated by Zeb2. [4] In neuronal development, Sip1 mutation in humans causes Mowat-Wilson syndrome, and Zeb2 controls the expression of genes regulating various aspects of neuronal development as shown in mouse models. [5] In atherosclerosis, Zeb2 regulates smooth muscle cell (SMC) phenotypic transition through chromatin remodeling. SMC-specific loss of Zeb2 in mice led to an inability of transitioning SMCs to turn off contractile programming and take on a fibroblast-like phenotype, but accelerated the formation of chondromyocytes, mirroring features of high-risk atherosclerotic plaques in human coronary arteries. [7]

References:

1. Dai, Dai, Gu, Shuangshuang, Han, Xiaxia, Vinuesa, Carola G, Shen, Nan. 2024. The transcription factor ZEB2 drives the formation of age-associated B cells. In Science (New York, N.Y.), 383, 413-421. doi:10.1126/science.adf8531. https://pubmed.ncbi.nlm.nih.gov/38271512/

2. De Coninck, Stien, Berx, Geert, Taghon, Tom, Van Vlierberghe, Pieter, Goossens, Steven. 2019. ZEB2 in T-cells and T-ALL. In Advances in biological regulation, 74, 100639. doi:10.1016/j.jbior.2019.100639. https://pubmed.ncbi.nlm.nih.gov/31383581/

3. Goto, Manaka, Takahashi, Hideyuki, Yoshida, Ryochi, Okamura, Tomohisa, Fujio, Keishi. 2024. Age-associated CD4+ T cells with B cell-promoting functions are regulated by ZEB2 in autoimmunity. In Science immunology, 9, eadk1643. doi:10.1126/sciimmunol.adk1643. https://pubmed.ncbi.nlm.nih.gov/38330141/

4. Epifanova, Ekaterina, Babaev, Alexey, Newman, Andrew G, Tarabykin, Victor. 2018. Role of Zeb2/Sip1 in neuronal development. In Brain research, 1705, 24-31. doi:10.1016/j.brainres.2018.09.034. https://pubmed.ncbi.nlm.nih.gov/30266271/

5. Birkhoff, Judith C, Huylebroeck, Danny, Conidi, Andrea. 2021. ZEB2, the Mowat-Wilson Syndrome Transcription Factor: Confirmations, Novel Functions, and Continuing Surprises. In Genes, 12, . doi:10.3390/genes12071037. https://pubmed.ncbi.nlm.nih.gov/34356053/

6. Gao, Xin, Shen, Qian, Roco, Jonathan A, Zaunders, John J, Cockburn, Ian A. 2024. Zeb2 drives the formation of CD11c+ atypical B cells to sustain germinal centers that control persistent infection. In Science immunology, 9, eadj4748. doi:10.1126/sciimmunol.adj4748. https://pubmed.ncbi.nlm.nih.gov/38330097/

7. Cheng, Paul, Wirka, Robert C, Shoa Clarke, Lee, Kundaje, Anshul, Quertermous, Thomas. 2022. ZEB2 Shapes the Epigenetic Landscape of Atherosclerosis. In Circulation, 145, 469-485. doi:10.1161/CIRCULATIONAHA.121.057789. https://pubmed.ncbi.nlm.nih.gov/34990206/

8. Hegarty, Shane V, Sullivan, Aideen M, O'Keeffe, Gerard W. 2015. Zeb2: A multifunctional regulator of nervous system development. In Progress in neurobiology, 132, 81-95. doi:10.1016/j.pneurobio.2015.07.001. https://pubmed.ncbi.nlm.nih.gov/26193487/