Core Services: Custom Animal Model Generation

iTL's primary business is the creation of bespoke rodent models tailored to the specific research goals of its clients. They offer a wide array of genetic modifications in both mice and rats.

Custom Mouse Models

The mouse remains the premier model organism for in vivo studies, and iTL provides a full spectrum of genetic modifications.

• Knockout (KO) Models: These models are created to inactivate or "knock out" a target gene to study its function.

  • Constitutive Knockouts: The target gene is permanently inactivated in all cells of the animal.
  • Conditional Knockouts (cKO): A more sophisticated model where the target gene is flanked by loxP sites. The gene functions normally until the mouse is crossed with a Cre recombinase-expressing line, allowing for gene inactivation in specific tissues or at specific times. This is crucial for studying genes that are essential for embryonic development.
  • KO-First Models: A versatile allele that initially functions as a gene knockout but can be converted to a conditional allele through Cre-mediated recombination.

• Knock-in (KI) Models: These models involve inserting a specific DNA sequence into a precise location in the mouse genome.

  • Point Mutations: Introducing specific, subtle mutations to study the effects of a single amino acid change, often to mimic a human disease-causing mutation.
  • Reporter & Tag Insertion: Inserting a reporter gene (e.g., EGFP, LacZ, mCherry) or an epitope tag (e.g., FLAG, HA) at a specific gene locus. This allows researchers to track the expression of their protein of interest or easily purify it.
  • Humanization: Replacing a mouse gene, or a portion of it, with its corresponding human counterpart. These "humanized" mice are invaluable tools for preclinical drug development, as they allow for the in vivo testing of therapies that target human-specific proteins.

• Transgenic Models: These models involve the introduction of a foreign gene (a transgene) into the mouse genome.

  • Targeted Transgenics: Inserting the transgene at a specific, well-characterized "safe harbor" locus like ROSA26. This ensures stable, predictable expression of the transgene without disrupting endogenous genes.
  • Random Insertion Transgenics: The traditional method where the transgene is injected into a pronucleus and integrates randomly into the genome.

Custom Rat Models

Recognizing the importance of the rat model for specific research areas like toxicology, cardiovascular disease, and neurobiology, iTL also provides custom gene targeting services for rats, including knockout and knock-in model generation.

Technology and Approach

iTL maintains expertise in multiple gene-editing technologies, allowing them to select the optimal method based on the complexity and goals of each project.

• Embryonic Stem (ES) Cell-Based Gene Targeting: The "gold standard" and traditional method for creating complex models like conditional knockouts and large knock-ins. iTL has over two decades of experience with this technique and utilizes its own proprietary, high-quality ES cell lines to ensure high rates of germline transmission.
• CRISPR/Cas9 Technology: A newer, highly efficient gene-editing tool used for generating knockouts, point mutations, and smaller knock-in projects. Its speed and efficiency make it a powerful option for many model types.

This dual expertise allows iTL's scientists to provide unbiased recommendations and design the most robust strategy for a client's project. The project workflow is highly collaborative, beginning with a free, in-depth consultation and strategy design phase, followed by model construction, rigorous quality control and validation, and final delivery of the confirmed animal models.

Supporting Services

To complement its model generation services, iTL also offers: * Cell Line Engineering: Applying the same gene-editing technologies to create custom-modified mammalian cell lines. * Colony Management: Providing services for breeding, maintaining, and expanding newly generated animal lines. * Cryopreservation: Safeguarding valuable custom lines through sperm or embryo cryopreservation.