International Mammalian Genome Society

logo18th International Mouse Genome Conference

17-22 October 2004, Seattle, USA


ORAL PRESENTATION

MONDAY OCTOBER 18

5.00pm – 5.15pm

INGENOTYPING – AN HIGHLY EFFICIENT APPROACH TO GENERATE GENE TARGETED MOUSE AND RAT MODELS

Laufs J, Sedlmeier R, Peters T, Huffstadt U, Wattler S, Nehls M

Ingenium Pharmaceuticals, Martinsried, Germany

Mouse and rats are the model of choice for in vivo studies of gene function but the development of knockouts and allelic variants, i.e. hypo – and hypermorphs, is time consuming and costly. The generation of mouse models is dominated by gene targeting through homologous recombination, which requires sophisticated ES cell manipulation and chimera production. No such standard procedure for the development of targeted rat models is available despite some first success in nuclear cloning of rats from unmodified somatic cells.  In order to make rat and mouse models with genetic alterations readily available to the scientific community, we developed a patented technology (named INGENOtypingTM) based on gene-saturating chemical mutagenesis. We first applied INGENOtypingTM to generate a pre-set library of mutagenized murine sperm that represents multiple alterations in every mouse gene. Currently somatic DNA and corresponding sperm samples of more than 15,000 mice derived from a well-controlled chemical mutagenesis process using ENU have been archived and can be screened for mutations in any gene of interest within days. Together with the subsequent extremely efficient in vitro fertilization, the adult heterozygous carriers are available within 3-4 months. This approach has now been adapted to rats for the industrialized production of gene targeted rat models.  ENU mutagenesis in our hands has resulted in more than 220 identified mouse mutations which are to a large extent null but also hypomorphic and hypermorphic alleles. The process and examples of ENU derived mutant mouse lines will be presented.

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