Specific and controlled modification of the mice genome has been made possible with the development of two new techniques: Homologous Recombination (HR) and the culture of Embryonic Stem (ES) cells. By using the ES cell-based HR method, one can specifically replace the targeted endogenous sequence with the lab-modified sequence, thereby achieving the programme modification of mouse genome. Using this ESC/HR-based gene targeting technology, Creative Biolabs is able to provide our clients with the most comprehensive list of genetically engineered models, including knock-out models and knock-in models.
Introduction of Embryonic Stem Cells
Since the isolation of Embryonic Stem (ES) cells from the culture of early mouse embryos was first reported in 1981, a new and efficient method for obtaining transgenic mice had been developed. These cells are genetically modified in vitro and then injected into a young embryo, which will give birth to chimeras due to their unique ability to colonize all the tissues of a host embryo including its germ line. The ES cell genotype cells could then be ''recycled'' in vivo and transmitted to future generations. Thus, by genetically modifying the genome of these cells, the corresponding modified mice could be obtained.
Introduction of Homologous Recombination (HR)
Mammalian cells have the enzymatic apparatus necessary for HR. Although the involved mechanisms haven't been fully elucidated yet, the successful development of gene targeting technologies allowing HR between an exogenous DNA and its cognate chromosomal sequence provides a powerful tool for generating mutant mouse strains with defined genetic modifications, even if this was relatively rare compared to the random integration of this same DNA.
In the knock-out strategy, the targeting vector includes a selection cassette inserted in an exon and is surrounded by regions of homology with the target gene. Homologous recombination occurs at the site of these homologous sequences, resulting in the creation of a null allele, where disruption of the target gene is induced by insertion of the selection cassette. At Creative Biolabs, we offer all kinds of knock-out models, including Conventional Knock-out Models, Conditional Knock-out Models, and KO First Models.
In the knock-in strategy, the target gene is replaced by the gene of interest. The choice of the sequences depends on the specific research purpose. Following homologous recombination with the chosen target gene, the modified allele expresses the sequences inserted in replacement of the endogenous gene. At Creative Biolabs, point mutations, reporter/tag genes, Cre recombinase, and human-specific genes can be introduced into specific sites to create the exact model you desire.
Meanwhile, Creative Biolabs is experienced in generating genetically engineered mouse models with the latest technologies that you may also be interested in:
Equipped with both seasoned specialists and cutting-edge technologies, Creative Biolabs is definitely a reliable research partner to discuss and design your ideal model to boost your next project and beyond. Please feel free to contact us or send an inquiry for more detailed information or a formal quote.
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