Transgenic Mouse Models
Precise and predictable gene targeting, only with ingenious.
|Transgenic Knockin to Your Gene of Interest||Safe-Harbor Transgenic Knockin|
|Express Cre, a reporter gene, or any sequence using your target gene’s promoter||Drive expression of a cDNA using a ubiquitous or tissue-specific promoter|
|Express a human cDNA in place of a mouse gene||Conditional cDNA overexpression, which you control using tissue-specific Cre lines|
|Express a modified version of a mouse gene to add a tag sequence or extra functional domain||Drug-inducible overexpression, controlled by administering doxycycline|
|Learn More||Learn More|
Transgenic mice have proven to be an invaluable research tool for studying human disease. At ingenious, we utilize precision gene targeting to generate your transgenic mouse. Our proprietary technologies allow for shorter production timelines and reduced costs when compared to other targeting methods, without compromising performance and quality.
Transgenic mice from ingenious are precisely targeted to create the model you need.
Faster production and lower prices.
Delivery of your germline-confirmed model is fully guaranteed.
Uses for Transgenic Models
Transgenic mice are utilized for an incredibly diverse range of experiments because this model type is so versatile. Using gene targeting to specifically target transgene insertion enables placement of your genetic construct at an exact location. Anything from the most faithful reporter line to a line for drug-inducible overexpression can be created using a transgenic knockin strategy.
History of Untargeted Transgenic Mice
Pronuclear injection of DNA can lead to low frequency integration of the sequence into the mouse genome at random sites. Extensive development of this method in the early 1980s made the creation of random-insertion transgenic mice a routine procedure. After potential founder mice are born they must be screened for germline transmission of the desired sequence. Ideally multiple alleles will be evaluated as expression of the transgene can be affected by its genomic position, and other genes can be disrupted if the transgene inserts within their sequence. Furthermore, multiple copies can randomly integrate into the genome – it may be necessary to screen a large number of mice until the appropriate founder has been identified.
In some cases the desired DNA sequence can be injected as a bacterial artificial chromosome (BAC) to alleviate some concerns with random insertion transgenesis. BACs can hold up to 200kb of sequence, which allows for large sequences such as entire genes or large promoters to be introduced into the mouse. Inserting an entire gene including introns, exons and regulatory sequences is beneficial when the coding sequence alone may not be sufficient for proper expression. The use of BAC transgenic constructs can result in more faithful gene regulation and processing as well as the potential to perform functional and regulatory studies on multiple transcripts.
Things to keep in mind when deciding if a pronuclear injection transgenic model is right for you:
- Random and unpredictable transgene integration and expression.
- Variable copy numbers of the transgene.
- Small transgenes may lack the cis-regulatory elements needed for proper expression .
- BAC constructs are harder to work with and require more molecular biology expertise.
- Need to screen founder mice (as opposed to ES cells). May not be 3Rs-friendly .
Consider Targeted Transgenics
Targeted transgenic approaches reduce or eliminate the downsides of random integration by pronuclear injection. Safe-harbor loci can be targeted by ingenious’ technologies to efficiently introduce your overexpression construct into the genome in a location where it will not interfere with other genes or be affected by the surrounding genetic environment.
To learn more about transgenic mice, speak with one of our scientific consultants today.
1) Sadelain M, Eirini PP, and Frederic DB. 2012. Safe Harbours for the Integration of New DNA in the Human Genome. Nature Reviews Cancer 12(1): 51-58.
2) Timeline for Transgenic Mice Analysis, University of Michigan
3) BAC recombineering and transgenesis, Vanderbilt University
4) What are the 3Rs? NC3RS