INGENOtyping®: Customer mouse models with unprecedented speed
Ingenium Pharmaceuticals AG provides state of the art mouse models through the INGENOtyping® library, a unique archive of pre-made mutant mouse models. The Jackson Laboratory provides innovative technologies to cost-effectively supply mice derived from this archive with unprecedented speed and reliability.
Fast delivery of knockouts and mouse models with other gene alterations
Ingenium Pharmaceuticals has established a comprehensive murine model library. The INGENOtyping® library encompasses over 300,000 unique mouse models each one carrying a gene-specific alteration (point mutation). All models are stored as sperm cells. Revitalization is performed via in vitro fertilization (IVF), a fast and reliable procedure, thereby circumventing the use of sophisticated ES cell manipulation and chimera production required by other standard technologies.
Generation of a mouse model is a simple Two-step Process
Step 1 Archive Screening
The models harboring the target gene specific mutations are identified by robust mutation screening technologies. Under industry standard confidentiality, the customer is providing the ID of the gene of interest. Ingenium's Scientists search the archive for mutations in less than one month through rapid screening of our DNA library and will provide a detailed bioinformatic mutation report listing and characterizing the identified alleles.
Step 2: Model Generation
Once you select the model or models of choice, The Jackson Laboratory will generate the line by in vitro fertilization. This step requires approximately 3 weeks to generate heterozygous newborns with a success rate of >98%. The mouse line can be delivered as heterozygous carriers about 6-8 weeks after birth. However, you might want to receive a homozygous line with or without phenotype data. Please contact The Jackson Laboratory to determine an applicable protocol to meet your research requirements.
Point mutations and allelic series as research tools: an example
For the examined Mc4r gene fragments, a total of five missense mutations that lead to an amino acid exchange in the polypeptide chain were identified in a library subset.
| Model | M-201a | M-201b | M-201c | M-201d | M-201e |
| Amino acid exchange | Ile 194 Phe | Tyr 302 Cys | Arg 147 Ser | Met 281 Lys | Tyr 21 His |
Predictive bioinformatic analysis indicated altered allelic activity in all five variants. These findings were ultimately confirmed by in vitro testing of receptor function (see below):
enlarged version of image available
From the five identified variants two alleles of the melanocortin-4 receptor, M-201a and M-201b, were further analyzed in vivo after model production using IVF. In vivo data confirmed the in vitro findings for both alleles versus wildtype (Grosse J. et al. 2006 N-ethyl-N-nitrosourea-based generation of mouse models for mutant G protein-coupled receptors. Physiol Genomics 26: 209-17.)
Relevance of the findings is supported by human in vivo data published recently in The New England Journal of Medicine (Farooqi I.S. et al. 2003. Clinical Spectrum of Obesity and Mutations in the Melanocortin 4 Receptor Gene. New England Journal of Medicine 348: 1085-95.)
Further technology publications:
Augustin M. et al. 2005. Efficient and fast targeted production of murine models based on ENU mutagenesis. Mamm Genome 16(6): 405-13.
Grosse J. et al. 2006. N-ethyl-N-nitrosourea-based generation of mouse models for mutant G protein-coupled receptors. Physiol Genomics 26: 209-17.
Peters T and Sedlmeier R. 2006. Current methods for high-throughput detection of novel DNA polymorphisms. Drug Discov Today: Technologies 3(2):123-29.
For further information please visit the Ingenium website at www.ingenium-ag.com
