Journal ArticleDOI
A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse.
Patrick M. Nolan,Josephine Peters,Mark A. Strivens,Derek C. Rogers,Jim J. Hagan,Nigel K. Spurr,Ian C. Gray,Lucie Vizor,D Brooker,E Whitehill,R Washbourne,Tertius Hough,Simon Greenaway,M Hewitt,Xue Zhong Liu,Stefan L. McCormack,K Pickford,R Selley,Christine A. Wells,Zuzanna Tymowska-Lalanne,P. Roby,Peter H. Glenister,C Thornton,Caroline Thaung,J A Stevenson,Ruth M. Arkell,Philomena Mburu,Rachel E. Hardisty,Amy E. Kiernan,Alexandra Erven,Karen P. Steel,Stéphanie Voegeling,Jean-Louis Guénet,Carole D. Nickols,R Sadri,M Nasse,Adrian M. Isaacs,Kay E. Davies,M Browne,Elizabeth M. C. Fisher,Joanne E. Martin,Sohaila Rastan,Steve D.M. Brown,Jackie Hunter +43 more
TLDR
A genome-wide, phenotype-driven screen for dominant mutations in the mouse is undertaken, which has led to a substantial increase in themouse mutant resource and represents a first step towards systematic studies of gene function in mammalian genetics.Abstract:
As the human genome project approaches completion, the challenge for mammalian geneticists is to develop approaches for the systematic determination of mammalian gene function. Mouse mutagenesis will be a key element of studies of gene function. Phenotype-driven approaches using the chemical mutagen ethylnitrosourea (ENU) represent a potentially efficient route for the generation of large numbers of mutant mice that can be screened for novel phenotypes. The advantage of this approach is that, in assessing gene function, no a priori assumptions are made about the genes involved in any pathway. Phenotype-driven mutagenesis is thus an effective method for the identification of novel genes and pathways. We have undertaken a genome-wide, phenotype-driven screen for dominant mutations in the mouse. We generated and screened over 26,000 mice, and recovered some 500 new mouse mutants. Our work, along with the programme reported in the accompanying paper, has led to a substantial increase in the mouse mutant resource and represents a first step towards systematic studies of gene function in mammalian genetics.read more
Citations
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Animal models of human disease: zebrafish swim into view.
TL;DR: This Review surveys the achievements and potential of zebrafish for modelling human diseases and for drug discovery and development.
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Assessing antidepressant activity in rodents: recent developments and future needs
TL;DR: This review focuses on recent findings regarding some of the most widely employed animal models used currently to predict antidepressant potential, and emphasis is placed on recent modifications to such paradigms that have increased their utility and reliability.
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The tail suspension test as a model for assessing antidepressant activity: review of pharmacological and genetic studies in mice.
TL;DR: The tail suspension test is a useful test for assessing the behavioural effects of antidepressant compounds and other pharmacological and genetic manipulations relevant to depression.
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The genetic architecture of quantitative traits
TL;DR: Complete genome sequences and improved technologies for polymorphism detection will greatly advance the genetic dissection of quantitative traits in model organisms, which will open avenues for exploration of homologous QTL in related taxa.
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Mammalian circadian biology: elucidating genome-wide levels of temporal organization.
TL;DR: The importance of maintaining the internal temporal homeostasis conferred by the circadian system is revealed by animal models in which mutations in genes coding for core components of the clock result in disease, including cancer and disturbances to the sleep/wake cycle.
References
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Journal ArticleDOI
Comprehensive observational assessment: Ia. A systematic, quantitative procedure for assessing the behavioral and physiologic state of the mouse.
TL;DR: With this method, the pattern profile of various classes of pharmacologic agents and their members can be identified and differentiated, and the relative specificity of their actions defined.
Journal ArticleDOI
Behavioral and functional analysis of mouse phenotype: SHIRPA, a proposed protocol for comprehensive phenotype assessment
Derek C. Rogers,Elizabeth M. C. Fisher,Steve D.M. Brown,Josephine Peters,A. J. Hunter,Joanne E. Martin +5 more
TL;DR: The SHIRPA procedure is developed, which utilizes standardized protocols for behavioral and functional assessment that provide a sensitive measure for quantifying phenotype expression in the mouse, and can be refined to test the function of specific neural pathways, which will contribute to a greater understanding of neurological disorders.
Journal ArticleDOI
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.
Journal ArticleDOI
Specific-locus test shows ethylnitrosourea to be the most potent mutagen in the mouse
TL;DR: Use of the specific-locus test to measure the frequency of transmitted gene mutations induced in mouse spermatogonia has shown ethylnitrosourea to be by far the most potent mutagen yet discovered in the mouse.
Journal ArticleDOI
Mouse ENU Mutagenesis
TL;DR: 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.
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