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Publication : Generation and Characterization of a TRIM21 Overexpressing Mouse Line.

First Author  Mehlmann LM Year  2024
Journal  Genesis Volume  62
Issue  5 Pages  e23616
PubMed ID  39487578 Mgi Jnum  J:360169
Mgi Id  MGI:7787230 Doi  10.1002/dvg.23616
Citation  Mehlmann LM, et al. (2024) Generation and Characterization of a TRIM21 Overexpressing Mouse Line. Genesis 62(5):e23616
abstractText  Specific removal of a protein is a key to understanding its function. "Trim-Away" utilizes TRIM21, an antibody receptor and ubiquitin ligase, for acute and specific reduction of proteins. When TRIM21 is expressed in cells, introduction of a specific antibody causes rapid degradation of the targeted protein; however, TRIM21 is endogenously expressed in few cell types. We have generated a mouse line using CRISPR to insert a conditional overexpression cassette of TRIM21 into the safe harbor site, Rosa26. These conditionally-expressing mice can be bred to a wide variety of Cre mice to target cell-specific TRIM21 overexpression in different tissues. Zp3(Cre) mice expressed TRIM21 protein specifically in oocytes, whereas Hprt(Cre) mice expressed the protein globally. When TRIM21-overexpressing oocytes were microinjected with specific antibodies targeting either the IP(3) receptor or SNAP23, these proteins were effectively degraded. In addition, cortical neural cells from globally-overexpressing TRIM21 mice showed a dramatic reduction in IP(3) receptor protein within hours after electroporation of a specific antibody. These experiments confirm the effectiveness of the Trim-Away method for protein reduction. These mice should make a valuable addition to the broader research community, as a wide range of proteins and cell types can be studied using this method.
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