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One key bottleneck in understanding the human genome is the relative under-characterization of 90% of protein coding regions. We report a collection of 1200 transgenic zebrafish strains made with the gene-break transposon (GBT) protein trap to simultaneously report and reversibly knockdown the tagged genes. Protein trap-associated mRFP expression shows previously undocumented expression of 35% and 90% of cloned genes at 2 and 4 days post-fertilization, respectively. Further, investigated alleles regularly show 99% gene-specific mRNA knockdown. Homozygous GBT animals in , , , and phenocopied established mutants. 204 cloned lines trapped diverse proteins, including 64 orthologs of human disease-associated genes with 40 as potential new disease models. Severely reduced skeletal muscle Ca transients in GBT homozygous animals validated the ability to explore molecular mechanisms of genetic diseases. This GBT system facilitates novel functional genome annotation towards understanding cellular and molecular underpinnings of vertebrate biology and human disease.
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http://dx.doi.org/10.7554/eLife.54572 | DOI Listing |
Int Immunopharmacol
September 2025
Key Laboratory for Biorheological Science and Technology of Chinese Ministry of Education, National Local Joint Engineering Lab for Vascular Implants, College of Bioengineering, Chongqing University, Chongqing 400044, China; JinFeng Laboratory, Chongqing, 401329, China. Electronic address: wanggx@cq
Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that plays a crucial role in the pathophysiology of asthma, initiating multiple allergic cascade responses. Tezepelumab is the only monoclonal antibody currently approved for marketing, which acts by blocking TSLP binding to TSLPR. However, it is reported that a TSLP trap which simultaneously block TSLP binding with TSLPR and IL-7Rα has better efficiency in the repression of TSLP signal pathway.
View Article and Find Full Text PDFImmunology
September 2025
Department of Biochemical Science and Technology, National Taiwan University, Taipei, Taiwan, ROC.
Enolase-1 (ENO1) is a moonlighting protein with multiple functions. When expressed on the cell surface, ENO1 binds plasminogen (PLG) and promotes cell migration by facilitating plasmin (PLM)-mediated extracellular matrix degradation. Here, we observed that inflammatory stimulation significantly upregulated ENO1 expression on the neutrophil surface, both in vitro and in vivo.
View Article and Find Full Text PDFPLoS One
September 2025
Children's Health Research Institute, Victoria Research Labs, London, Ontario, Canada.
Loss of actin cytoskeleton control can hinder integral developmental and physiological processes and can be the basis for a subset of developmental defects. SHROOM3 is an actin binding protein, best characterized as being essential for neural tube closure in vertebrates. Shroom3 expression has also been identified in the developing heart, with some associated congenital heart defects.
View Article and Find Full Text PDFFood Sci Biotechnol
October 2025
Department of Herbal Medicine, College of Pharmacy, Wonkwang University, 460 Iksandae-Ro, Iksan, Jeonbuk 54538 Republic of Korea.
Lycii fructus (LF) is widely used in traditional Asian medicine and as a dietary supplement due to its potential health benefits. Zeaxanthin (ZEA), a key carotenoid in LF, is crucial in supporting eye health. However, the effects of LF and ZEA on receptor activator of NF-kappaB Ligand (RANKL)-mediated osteoclast differentiation were not confirmed.
View Article and Find Full Text PDFCell Physiol Biochem
September 2025
Department of General Practice, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China, E-Mail:
Background/aims: Ubiquitin D (UBD), a member of the ubiquitin-like modifier (UBL) family, is significantly overexpressed in various cancers and is positively correlated with tumor progression. However, the role and underlying mechanisms of UBD in rheumatoid arthritis (RA) remain poorly understood. This study aimed to investigate the effects of UBD knockdown on the progression of RA.
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