The large-scale Munich ENU-mouse-mutagenesis screen

2000 ◽  
Vol 11 (7) ◽  
pp. 507-510 ◽  
Author(s):  
Dian Soewarto ◽  
Christiane Fella ◽  
Andreas Teubner ◽  
Birgit Rathkolb ◽  
Walter Pargent ◽  
...  
Keyword(s):  
Large Scale ◽  
Mutagenesis Screen ◽  
Mouse Mutagenesis

Feasibility for a large scale mouse mutagenesis by injecting CRISPR/Cas plasmid into zygotes

2013 ◽  
Vol 56 (1) ◽  
pp. 122-129 ◽  
Author(s):  
Daisuke Mashiko ◽  
Samantha A. M. Young ◽  
Masanaga Muto ◽  
Hirotaka Kato ◽  
Kaori Nozawa ◽  
...  
Keyword(s):  
Large Scale ◽  
Mouse Mutagenesis

Capitalizing on large-scale mouse mutagenesis screens

2000 ◽  
Vol 1 (2) ◽  
pp. 109-115 ◽  
Author(s):  
Monica J. Justice
Keyword(s):  
Large Scale ◽  
Mouse Mutagenesis

ENU-mouse mutagenesis screen: In search of animal models of psychiatric disorders

2004 ◽  
Vol 36 (05) ◽  
Author(s):  
F Ohl ◽  
EB Binder ◽  
A Rödel ◽  
P Weißenbacher ◽  
ME Keck
Keyword(s):  
Animal Models ◽  
Psychiatric Disorders ◽  
Mutagenesis Screen ◽  
Mouse Mutagenesis

Diabetes models by screen for hyperglycemia in phenotype-driven ENU mouse mutagenesis projects

2008 ◽  
Vol 294 (2) ◽  
pp. E232-E240 ◽  
Author(s):  
Bernhard Aigner ◽  
Birgit Rathkolb ◽  
Nadja Herbach ◽  
Martin Hrabé de Angelis ◽  
Rüdiger Wanke ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Large Scale ◽  
Experimental Models ◽  
Targeted Mutagenesis ◽  
Causative Mutation ◽  
Chromosomal Assignment ◽  
Screen Parameter ◽  
Mouse Mutants ◽  
Novel Alleles ◽  
Mouse Mutagenesis

More than 150 million people suffer from diabetes mellitus worldwide, and this number is expected to rise substantially within the next decades. Despite its high prevalence, the pathogenesis of diabetes mellitus is not completely understood. Therefore, appropriate experimental models are essential tools to gain more insight into the genetics and pathogenesis of the disease. Here, we describe the current efforts to establish novel diabetes models derived from unbiased, phenotype-driven, large-scale N-ethyl- N-nitrosourea (ENU) mouse mutagenesis projects started a decade ago using hyperglycemia as a high-throughput screen parameter. Mouse lines were established according to their hyperglycemia phenotype over several generations, thereby revealing a mutation as cause for the aberrant phenotype. Chromosomal assignment of the causative mutation and subsequent candidate gene analysis led to the detection of the mutations that resulted in novel alleles of genes already known to be involved in glucose homeostasis, like glucokinase, insulin 2, and insulin receptor. Additional ENU-induced hyperglycemia lines are under genetic analysis. Improvements in screen for diabetic animals are implemented to detect more subtle phenotypes. Moreover, diet challenge assays are being employed to uncover interactions between genetic and environmental factors in the pathogenesis of diabetes mellitus. The new mouse mutants recovered in phenotype-driven ENU mouse mutagenesis projects complement the available models generated by targeted mutagenesis of candidate genes, all together providing the large resource of models required for a systematic dissection of the pathogenesis of diabetes mellitus.

Screening for increased plasma urea levels in a large-scale ENU mouse mutagenesis project reveals kidney disease models

2007 ◽  
Vol 292 (5) ◽  
pp. F1560-F1567 ◽  
Author(s):  
Bernhard Aigner ◽  
Birgit Rathkolb ◽  
Nadja Herbach ◽  
Elisabeth Kemter ◽  
Christina Schessl ◽  
...  
Keyword(s):  
Large Scale ◽  
Kidney Diseases ◽  
Weight Ratio ◽  
Mouse Strains ◽  
Chemical Parameters ◽  
Plasma Urea ◽  
Glomerular Lesions ◽  
Successful Establishment ◽  
Mutant Lines ◽  
Mouse Mutagenesis

Kidney diseases lead to the failure of urinary excretion of metabolism products. In the Munich ethylnitrosourea (ENU) mouse mutagenesis project, which is done on a C3H inbred genetic background, blood samples of more than 15,000 G1 offspring and 500 G3 pedigrees were screened for alterations in clinical-chemical parameters. We identified 44 animals consistently exhibiting increased plasma urea concentrations. Transmission analysis of the altered phenotype of 23 mice to subsequent generations led to the establishment of five mutant lines. Both sexes were affected in these lines. Urinary urea levels were decreased in the mutants. In addition, most mutants showed increased plasma and decreased urinary creatinine levels. Pathological investigation of kidneys from the five mutant lines revealed a broad spectrum of alterations, ranging from no macroscopic and light microscopic kidney alterations to decreased kidney weight-to-body weight ratio, dilation of the renal pelvis, and severe glomerular lesions. Thus screening for elevated plasma urea levels in a large-scale ENU mouse mutagenesis project resulted in the successful establishment of mouse strains which are valuable tools for molecular studies of mechanisms involved in urea excretion or which represent interesting models for kidney diseases.

scholarly journals Shotgun Cloning of Transposon Insertions in the Genome ofCaenorhabditis elegans

2004 ◽  
Vol 5 (3) ◽  
pp. 225-229 ◽  
Author(s):  
Alexander M. van der Linden ◽  
Ronald H. A. Plasterk
Keyword(s):  
Transposable Elements ◽  
Large Scale ◽  
Insertional Mutagenesis ◽  
Genomic Sequence ◽  
Mutagenesis Screen ◽  
Mutator Strain ◽  
C Elegans ◽  
Large Numbers ◽  
Transposon Insertions ◽  
Insertional Mutagenesis Screen

We present a strategy to identify and map large numbers of transposon insertions in the genome ofCaenorhabditis elegans. Our approach makes use of the mutator strainmut-7, which has germline-transposition activity of the Tc1/mariner family of transposons, a display protocol to detect new transposon insertions, and the availability of the genomic sequence ofC. elegans. From a pilot insertional mutagenesis screen, we have obtained 351 new Tc1 transposons inserted in or near 219 predictedC. elegansgenes. The strategy presented provides an approach to isolate insertions of natural transposable elements in manyC. elegansgenes and to create a large-scale collection ofC. elegansmutants.

PHENOSITE: A WEB DATABASE INTEGRATING THE MOUSE PHENOTYPING PLATFORM AND THE EXPERIMENTAL PROCEDURES IN MICE

2007 ◽  
Vol 05 (06) ◽  
pp. 1173-1191 ◽  
Author(s):  
HIROSHI MASUYA ◽  
SUMI YOSHIKAWA ◽  
NAOHIKO HEIDA ◽  
TETSURO TOYODA ◽  
SHIGEHARU WAKANA ◽  
...  
Keyword(s):  
Large Scale ◽  
Chromosomal Location ◽  
Web Database ◽  
Phenotypic Data ◽  
Resource Information ◽  
Related Information ◽  
Mouse Mutants ◽  
Experimental Protocols ◽  
Using Data ◽  
Mouse Mutagenesis

Recently, a number of collaborative large-scale mouse mutagenesis programs have been launched. These programs aim for a better understanding of the roles of all individual coding genes and the biological systems in which these genes participate. In international efforts to share phenotypic data among facilities/institutes, it is desirable to integrate information obtained from different phenotypic platforms reliably. Since the definitions of specific phenotypes often depend on a tacit understanding of concepts that tends to vary among different facilities, it is necessary to define phenotypes based on the explicit evidence of assay results. We have developed a website termed PhenoSITE (Phenome Semantics Information with Terminology of Experiments: ), in which we are trying to integrate phenotype-related information using an experimental-evidence–based approach. The site's features include (1) a baseline database for our phenotyping platform; (2) an ontology associating international phenotypic definitions with experimental terminologies used in our phenotyping platform; (3) a database for standardized operation procedures of the phenotyping platform; and (4) a database for mouse mutants using data produced from the large-scale mutagenesis program at RIKEN GSC. We have developed two types of integrated viewers to enhance the accessibility to mutant resource information. One viewer depicts a matrix view of the ontology-based classification and chromosomal location of each gene; the other depicts ontology-mediated integration of experimental protocols, baseline data, and mutant information. These approaches rely entirely upon experiment-based evidence, ensuring the reliability of the integrated data from different phenotyping platforms.

scholarly journals N-Ethyl-N-Nitrosourea Mutagenesis of a 6- to 11-cM Subregion of the Fah–Hbb Interval of Mouse Chromosome 7: Completed Testing of 4557 Gametes and Deletion Mapping and Complementation Analysis of 31 Mutations

Genetics ◽  
1999 ◽  
Vol 152 (1) ◽  
pp. 373-383 ◽  
Author(s):  
Eugene M Rinchik ◽  
Donald A Carpenter
Keyword(s):  
Mouse Chromosome ◽  
Large Scale ◽  
Mouse Genome ◽  
Chemical Mutagenesis ◽  
Deletion Mapping ◽  
Allelic Series ◽  
Mutagenesis Screen ◽  
Recessive Mutations ◽  
Radiation Induced ◽  
Complementation Groups

Abstract An interval of mouse chromosome (Chr) 7 surrounding the albino (Tyr; c) locus, and corresponding to a long 6- to 11-cM Tyr deletion, has been the target of a large-scale mutagenesis screen with the chemical supermutagen N-ethyl-N-nitrosourea (ENU). A segment of Chr 7, from a mutagenized genome bred from ENU-treated males, was made hemizygous opposite the long deletion for recognition and recovery of new recessive mutations that map within the albino deletion complex. Over 6000 pedigrees were analyzed, and 4557 of these were completely tested for mutations specifying both lethal and gross visible phenotypes. Thirty-one nonclustered mutations were identified and assigned to 10 complementation groups by pairwise trans-complementation crosses. Deletion-mapping analyses, using the extensive series of radiation-induced Tyr deletions, placed the loci defined by each of these complementation groups into defined intervals of the Tyr-region deletion map, which facilitates the identification of each locus on physical and transcription maps of the region. These mutations identified seven new loci and provided new ENU-induced alleles at three previously defined loci. Interestingly, no mutations were recovered that recapitulated three phenotypes defined by analysis of homozygous or partially complementing albino deletions. On the basis of our experience with this screen, we discuss a number of issues (e.g., locus mutability, failure to saturate, number of gametes to screen, allelic series) of concern when application of chemical mutagenesis screens to megabase regions of the mouse genome is considered.

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