Mouse ENU Mutagenesis
TLDR
O Ongoing mouse ENU mutagenesis experiments are generating a treasure trove of new mutations to allow an in-depth study of a single gene, a chromosomal region or a biological system.Abstract:
The progress of human genome sequencing is driving genetic approaches to define gene function. Strategies such as gene traps and chemical mutagenesis will soon generate a large mutant mouse resource. Point mutations induced by N -ethyl- N -nitrosourea (ENU) provide a unique mutant resource because they: (i) reflect the consequences of single gene change independent of position effects; (ii) provide a fine-structure dissection of protein function; (iii) display a range of mutant effects from complete or partial loss of function to exaggerated function; and (iv) discover gene functions in an unbiased manner. Phenotype-driven ENU screens in the mouse are emphasizing relevance to human clinical disease by targeting cardiology, physiology, neurology, immunity, hematopoiesis and mammalian development. Such approaches are extremely powerful in understanding complex human diseases and traits: the base-pair changes may accurately model base changes found in human diseases, and subtle mutant alleles in a standard genetic background provide the ability to analyze the consequences of compound genotypes. Ongoing mouse ENU mutagenesis experiments are generating a treasure trove of new mutations to allow an in-depth study of a single gene, a chromosomal region or a biological system.read more
Citations
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Genetic analysis of host resistance: Toll-like receptor signaling and immunity at large
Bruce Beutler,Zhengfan Jiang,Philippe Georgel,Karine Crozat,Ben A. Croker,Sophie Rutschmann,Xin Du,Kasper Hoebe +7 more
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Genome-wide, large-scale production of mutant mice by ENU mutagenesis
M. Hrabe de Angelis,Heinrich Flaswinkel,Helmut Fuchs,Birgit Rathkolb,Dian Soewarto,S. Marschall,Stephan Heffner,Walter Pargent,K. Wuensch,M. Jung,André Reis,Thomas Richter,Francesca Alessandrini,Thilo Jakob,Edith Fuchs,Hubert Kolb,Elisabeth Kremmer,K. Schaeble,B. Rollinski,Adelbert A. Roscher,Christoph Peters,Thomas Meitinger,T. M. Strom,Thomas Steckler,Florian Holsboer,Thomas Klopstock,F. Gekeler,C. Schindewolf,Thomas S. Jung,Karen B. Avraham,Heidrun Behrendt,Johannes Ring,Andreas Zimmer,Klaus Schughart,Klaus Pfeffer,Eckhard Wolf,Rudi Balling +36 more
TL;DR: In screening over 14,000 mice for a large number of clinically relevant parameters, 182 mouse mutants are recovered and this mutagenesis screen leads to a significant increase in the number of mouse models available to the scientific community.
References
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Journal ArticleDOI
Positional cloning of the mouse circadian clock gene.
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