Humanized Mice

Humanized Mice from GeneTargeting.comMouse models provide the research community with an indispensable tool for studying human disease, with over 15,000 orthologous genes between the mouse and human genomes (Church et al 2009). Traditional approaches to humanize the mouse manipulate only the coding regions of the genes of interest. Recent research has demonstrated that non-coding regions of the genome have implications in gene regulation and function that the scientific community is only beginning to understand. Therefore, it is becoming increasingly important to include non-coding regions of a human gene of interest when targeting the mouse gene ortholog.

Introducing ingenious’ TruHumanization™

ingenious now offers TruHumanization™ as a solution to the challenges presented by standard methods to humanize the mouse. This technology utilizes large BACs, enabling ingenious to replace the mouse gene with the entire human gene sequence including promoter, intron, exon, and regulatory sequences. These large insertions can be done with a single targeting step, saving researchers time and money. This leads to more faithful gene regulation and processing as well as the potential to perform functional and regulatory studies on multiple transcripts.

Traditional Methods of Humanizing the Mouse

  • The creation of single or multiple human point mutations within a homologous mouse gene, which mimic those seen in the relevant human disease of study.

  • Replacement of a mouse exon with the human homolog, allowing the expression of a chimeric mouse-human protein in vivo.

  • Insertion of a human cDNA to replace a mouse gene, allowing expression of the human protein within the context of the mouse.

  • Conditional activation of a human cDNA from the mouse Rosa26 locus, allowing more specific control of expression of the relevant human protein in the mouse model.

Enhanced Capabilities

  • Addition of F.A.S.T.™ cassette will enable inducible/reversible control of human gene.

  • Addition of reporters or tags for co-expression with human protein.

After You Receive Your Mice

ingenious provides the advanced technology options to address projects of virtually any size, but our services do not end there. Once you receive your model, you will need to generate a cohort of mice to utilize for experiments. ingenious’ post project support services provides the tools you need for cohort development, as well as cryopreservation services for protecting your investment.

Resources for Further Reading

  • Church DM et al. Lineage-specific biology revealed by a finished genome assembly of the mouse. PLoS Biol. 2009 May 5; 7(5): e1000112.

  • Devoy A et al. Genomically humanized mice: technologies and promises. Nat Rev Genet. 2011 Dec 16; 13(1): 14-20.

  • Macdonald LE et al. Precise and in situ genetic humanization of 6Mb of mouse immunoglobulin genes. Proc Natl Acad Sci USA. 2014 Apr 8; 11(14): 5147-52.

  • ENCODE (ENCyclopedia Of DNA Elements): The goal of this international database is to map functional elements within the human genome to the biological functions they regulate.