Mammalian Genome

Balling, Rudi ; Brown, Steve ; Hrabe de Angelis, Martin ; Justice, Monica ; Nadeau, Joe ; Peters, Jo

doi: 10.1007/s003350010091pmid: N/A

Wells, Christine ; Brown, Steve D.M.

doi: 10.1007/s003350010092pmid: 10886008

Phenotype-driven mutagenesis approaches in the mouse will deliver a vastly expanded mouse mutant resource and can be expected to lead to the identification of novel genes and pathways, enabling the emergence of new insights into mammalian gene function. In order for this goal to be realized, developments in genomics need to be harnessed to progress in mouse mutagenesis. We need firstly to generate a mutant map of the mouse, devising and employing rapid methods for the genetic mapping of the growing mouse mutant resource. Secondly, we need to be able to rapidly identify and assess candidate genes in the vicinity of the mapped mutations. Developments in mapping and genotyping technology are described that will potentially speed the construction of a rich mutant map of the mouse. In addition, the benefits of comparative sequencing of the human and mouse genomes are reviewed. The availability of both human and mouse genome sequences will underpin the evolution of a comprehensive and well annotated mammalian gene map that will significantly enhance our ability to move rapidly from mapped mutation to the identification of the underlying gene.

Noveroske, J.K. ; Weber, J.S. ; Justice, M.J.

doi: 10.1007/s003350010093pmid: 10886009

Justice, Monica J. ; Carpenter, Don A. ; Favor, Jack ; Neuhauser-Klaus, Angelika ; Hrabé de Angelis, Martin ; Soewarto, Dian ; Moser, Amy ; Cordes, Sabine ; Miller, Darla ; Chapman, Verne ; Weber, John S. ; Rinchik, Eugene M. ; Hunsicker, Patricia R. ; Russell, William L. ; Bode, Vernon C.

Rinchik, Eugene M.

doi: 10.1007/s003350010095pmid: 10886011

Because the mouse has become the pre-eminent model system for functional genomics and analysis of complex-systems/pathways in mammals, there has been an escalation of interest in the generation and analysis of mouse mutations to use as tools in these analyses. I argue here for a parallel investment in continuing the development of appropriately marked chromosomal rearrangements to use as genetic reagents in mutation recovery, analysis, and maintenance crosses. Specifically, visibly marked interstitial chromosomal deletions can be valuable for regional mutagenesis screens for recessives based on hemizygosity, and they can also be used to simplify genetic fine-mapping as a prelude to gene identification based on positional cloning/candidacy strategies. Dominantly marked chromosomal inversions that also manifest some kind of recessive phenotype can be exploited in more extensive regional mutagenesis screens based on homozygosity, and are invaluable for simplified, low-cost and error-reduced mutant-stock maintenance. Also discussed are several issues concerning genetic background, particularly from the point of view of genetic-reagent resource development.

Nolan, Patrick M. ; Peters, Jo ; Vizor, Lucie ; Strivens, Mark ; Washbourne, Rebecca ; Hough, Tertius ; Wells, Christine ; Glenister, Peter ; Thornton, Claire ; Martin, Jo ; Fisher, Elizabeth ; Rogers, Derek ; Hagan, Jim ; Reavill, Charlie ; Gray, Ian ;

Soewarto, Dian ; Fella, Christiane ; Teubner, Andreas ; Rathkolb, Birgit ; Pargent, Walter ; Heffner, Stephan ; Marschall, Susan ; Wolf, Eckhard ; Balling, Rudi ; Hrabé de Angelis, Martin

doi: 10.1007/s003350010097pmid: 10886013

Knapik, Ela W.

doi: 10.1007/s003350010098pmid: 10886014

Favor, Jack ; Neuhäuser-Klaus, Angelika

doi: 10.1007/s003350010099pmid: 10886015

We have summarized our extensive series of mutagenesis experiments to isolate dominant mutations in the mouse that express eye morphological defects. Thirty-two experimental groups in which parental mice were exposed to chemical mutagens or irradiation and a historical control group of the laboratory are presented. The largest series of experiments included parental exposure to ethylnitrosourea or irradiation. A total of 203 dominant mutants were confirmed among 456,890 offspring screened, which represents one of the largest collections of mutations in the mouse affecting one organ following a systematic screen of offspring of mutagenized animals. The largest group of mutations (92) was recovered in offspring of parental mice exposed to ethylnitrosourea. The second largest group of mutations (62) was recovered in irradiation experiments. Fifty-six mutations recovered in ethylnitrosourea experiments have been mapped to 22 loci. The affected genes have been identified for a number of the recovered mutations including Cryga, Crygb, Cgyge, Pax6, Pax2, Mitf, Lim2, and Cx50. On the basis of our experiences, a number of considerations when undertaking such screens are discussed, including a) choice of mutagen, b) experimental design, and c) the criteria for such experiments to ensure that mutations at novel loci will be recovered.

Flaswinkel, Heinrich ; Alessandrini, Francesca ; Rathkolb, Birgit ; Decker, Tanja ; Kremmer, Elisabeth ; Servatius, Angela ; Jakob, Thilo ; Soewarto, Dian ; Marschall, Susan ; Fella, Christiane ; Behrendt, Heidrun ; Ring, Johannes ; Wolf, Eckhard ; Balling, Rudi ; Hrabé de Angelis, Martin ;