AI Article Synopsis
- Studying essential genes in live mice is difficult due to irreversible genetic changes and slow protein depletion.
- The first-generation auxin-inducible-degron (AID) system works well for cultured cells but is toxic to mice, limiting its use.
- The optimized second-generation AID system allows for conditional loss of key protein CEP192 in mice without toxicity, enabling rapid and sustained protein depletion for better understanding of protein function.
Article Abstract
Studying essential genes required for dynamic processes in live mice is challenging as genetic perturbations are irreversible and limited by slow protein depletion kinetics. The first-generation auxin-inducible-degron (AID) system is a powerful tool for analyzing inducible protein loss in cultured cells. However, auxin administration is toxic to mice, preventing its long-term use in animals. Here, we use an optimized second-generation AID system to achieve the conditional and reversible loss of the essential centrosomal protein CEP192 in live mice. We show that the auxin derivative 5-Ph-IAA is well tolerated over two weeks and drives near-complete CEP192-mAID degradation in less than one hour . Prolonged CEP192 loss led to cell division failure and cell death in proliferative tissues. Thus, the second-generation AID system is well suited for rapid and/or sustained protein depletion in live mice, offering a valuable new tool for interrogating protein function .
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11185741 | PMC |
| http://dx.doi.org/10.1101/2024.06.04.597287 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Heterogeneity in Fluorescence-Stained Sperm Membrane Patterns and Their Dynamic Changes Towards Fertilization in Mice.
Front Biosci (Landmark Ed)
January 2025
Graduate School of Life and Environmental Sciences, Integrated Graduate School of Medicine, Engineering, and Agricultural Sciences, University of Yamanashi, 400-8510 Kofu, Japan.
Background: Sperm represent a heterogeneous population crucial for male reproductive success. Additionally, sperm undergo dynamic changes during maturation and capacitation. Despite these well-established processes, the complex nature of sperm heterogeneity and membrane dynamics remains elusive.
View Article and Find Full Text PDFEnhanced Immunogenicity and Affinity with A35R-Fc-Based Chimeric Protein Compared to MPXV A35R Protein.
Viruses
January 2025
School of Public Health, Bengbu Medical University, Bengbu 233030, China.
The re-emergence of the mpox pandemic poses considerable challenges to human health and societal development. There is an urgent need for effective prevention and treatment strategies against the mpox virus (MPXV). In this study, we focused on the A35R protein and created a chimeric A35R-Fc protein by fusing the Fc region of IgG to its C-terminal.
View Article and Find Full Text PDFGenetic and Molecular Characterization of Avian Influenza A(H9N2) Viruses from Live Bird Markets (LBM) in Senegal.
Viruses
January 2025
Département de Virologie, Institut Pasteur de Dakar, Dakar BP 220, Senegal.
Despite extensive experience with influenza surveillance in humans in Senegal, there is limited knowledge about the actual situation and genetic diversity of avian influenza viruses (AIVs) circulating in the country, hindering control measures and pandemic risk assessment. Therefore, as part of the "One Health" approach to influenza surveillance, we conducted active AIV surveillance in two live bird markets (LBMs) in Dakar to better understand the dynamics and diversity of influenza viruses in Senegal, obtain genetic profiles of circulating AIVs, and assess the risk of emergence of novel strains and their transmission to humans. Cloacal swabs from poultry and environmental samples collected weekly from the two LBMs were screened by RT-qPCR for H5, H7, and H9 AIVs.
View Article and Find Full Text PDFStudying the Oncolytic Activity of Strains Against Hepatoma, Glioma, and Pancreatic Cancer and .
Microorganisms
January 2025
Scientific and Educational Center, Molecular Bases of Interaction of Microorganisms and Human of the Center for Personalized Medicine of Federal State Budgetary Scientific Institution, Institute of Experimental Medicine, Acad. Pavlov Street, 12, 197022 Saint Petersburg, Russia.
Background: Cancer remains a leading cause of mortality globally. Conventional treatment modalities, including radiation and chemotherapy, often fall short of achieving complete remission, highlighting the critical need for novel therapeutic strategies. One promising approach involves the oncolytic potential of Group A (GAS) strains for tumor treatment.
View Article and Find Full Text PDFZY15 Alleviates Intestinal Inflammation and Barrier Dysfunction via AKT/mTOR/HIF-1α/RORγt/IL-17 Signaling and the Gut Microbiota in ETEC K88-Challenged .
Antioxidants (Basel)
January 2025
Key Laboratory of Feed Biotechnology of Ministry of Agriculture and Rural Affairs, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
, a recognized probiotic, improves intestinal health in animals, but the mechanism remains unclear. This study investigates the mechanisms by which ZY15, isolated from healthy pig feces, mitigates intestinal barrier damage and inflammation caused by oxidative stress in Enterotoxigenic (ETEC) K88-challenged mice. The results indicated that ZY15 increased antioxidant capacity by reducing serum reactive oxygen species (ROS) and superoxide dismutase (SOD) levels.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!