Generation of Gene Humanized Mouse Model

Identification of in vivo models is a natural prediction for special areas of human research that may be challenging due to the divergence between species.

Mice have become the most commonly used mammalian models for studying human physiology or disease. Many well characterized inbred lines and transgenic mouse trains have been established. Mice are relatively easy to maintain, and the generation time is short. They share a number of physiological characteristics and similar diseases with humans naturally or experimentally. Both mouse and human genomes have been sequenced and identified as humanized mouse genes corresponding to most human genes.

The technological achievements make the generation of the gene humanized mouse models

Another important reason for the popularity of mouse as an organism is the ability to operate the mouse genome. The first transgenic mice were generated by randomly inserting DNA into the mouse genome a few decades ago. And random transgene insertion through microinjection of DNA into fertilized eggs to generate gene modified mouse model is still common today. In this aspect, the key development is the isolation and establishment of mouse embryonic stem (ES) cell lines, as well as the discovery and application of targeted genes to ES cells. Mouse ES cells are pluripotent cells that maintain the ability to promote the development of all cell lines in the culture of mouse embryos.

Targeting gene controls a natural cellular repair mechanism—homologous recombination (HR). And identical DNA molecules exchange nucleotide sequences. When designed exogenous DNA molecules are introduced into ES cells and the exchange occurs in relatively low frequency level.

In 2007, Mario Capecchi, Martin Evans and Oliver Smithies won the Nobel Prize in physiology and medicine prize through the use of embryonic stem cells into specific gene modified principle admitted they have combine the discovery of huge influence on scientific research. Their discovery opens the door for researchers to perform ES cell targeting genes and thousands of mouse strains.

The introduction of site specific recombinant enzymes (SSRs) is a further progression. For example, Cre, Flp, wC31 and recombinant enzyme are as gene modification tools in mammalian cells. In addition to the other things, SSRs has allowed for the correct choice of target to ES cell clones used marker gene deletion in a particular cell type or developmental stage.

In the past thirty years, our ability to generate gene humanized mouse models has become more and more complex. Hope this article will provide useful guidance for such type of decision.

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