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| http://dx.doi.org/10.1104/pp.112.196105 | DOI Listing |
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Lessons learned from the Eµ-TCL1 mouse model of CLL.
Semin Hematol
June 2024
Department of Molecular Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address:
The Eµ-TCL1 mouse model has been used for over 20 years to study the pathobiology of chronic lymphocytic leukemia (CLL) and for preclinical testing of novel therapies. A CLL-like disease develops with increasing age in these mice due to a B cell specific overexpression of human TCL1. The reliability of this model to mirror human CLL is controversially discussed, as none of the known driver mutations identified in patients are found in Eµ-TCL1 mice.
View Article and Find Full Text PDFA word of caution: T-DNA-associated mutagenesis in plant reproduction research.
J Exp Bot
June 2024
Horticell, Department of Plants and Crops, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000 Ghent, Belgium.
T-DNA transformation is prevalent in Arabidopsis research and has expanded to a broad range of crops and model plants. While major progress has been made in optimizing the Agrobacterium-mediated transformation process for various species, a variety of pitfalls associated with the T-DNA insertion may lead to the misinterpretation of T-DNA mutant analysis. Indeed, secondary mutagenesis either on the integration site or elsewhere in the genome, together with epigenetic interactions between T-DNA inserts or frequent genomic rearrangements, can be tricky to differentiate from the effect of the knockout of the gene of interest.
View Article and Find Full Text PDFGene therapy for age-related macular degeneration: potential, feasibility, and pitfalls.
Curr Opin Ophthalmol
May 2024
Vanderbilt University Medical Center, Department of Ophthalmology, Nashville, Tennessee, USA.
Purpose Of Review: The landscape for age-related macular degeneration (AMD) is rapidly changing with addition of biosimilars and now United States Food and Drug Administration (FDA) approved nonneovascular AMD (nnAMD) treatment options. These developments have inspired a burgeoning pipeline of gene therapy approaches focused on similar antivascular endothelial growth factors (VEGF) and complement related pathways. Historic and more recent setbacks in the gene therapy pipeline, including intraocular inflammatory reactions, have raised important concerns for adverse events related to AMD therapeutics both for gene and nongene approaches.
View Article and Find Full Text PDFTackling Tissue Macrophage Heterogeneity by SplitCre Transgenesis.
Methods Mol Biol
August 2023
Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot, Israel.
Macrophages represent a broad spectrum of distinct, but closely related tissue-resident immune cells. This presents a major challenge for the study of functional aspects of these cells using classical Cre recombinase-mediated conditional mutagenesis in mice, since single promoter-driven Cre transgenic models often display limited specificity toward their intended target. The advent of CRISPR/Cas9 technology has now provided a time- and cost-effective method to explore the full potential of binary transgenic, intersectional genetics.
View Article and Find Full Text PDFLimitations of human tau-expressing mouse models and novel approaches of mouse modeling for tauopathy.
Front Neurosci
April 2023
Department of Functional Brain Imaging, Institute for Quantum Medical Sciences, National Institutes for Quantum Science and Technology, Chiba, Japan.
Neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein are primarily neuropathological features of a number of neurodegenerative diseases, collectively termed tauopathy. There is no disease-modifying drug available for tauopathy except anti-amyloid antibody therapies for Alzheimer's disease. For tau-targeting therapy, experimental models recapitulating human tau pathologies are indispensable.
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