Genetically Engineered Mouse Models (GEMM)

Overview of Genetically Engineered Mouse Models (GEMM)

Research has found that overexpression, deletion, or mutation of a certain gene can lead to spontaneous tumor development in mice. Through the genetic engineering methods mentioned above, tumors in mice can be artificially induced. Therefore, we can artificially establish genetically engineered mouse cancer models (GEMM) and conduct a series of tumor-related studies based on these mouse models. Nowadays, GEMM is increasingly becoming a powerful and indispensable tool for us to validate clinical findings and deepen our understanding of cancer mechanisms.

Methods to Generate the GEMMs

Numerous methods have been developed to create GEMMs including the transgenic approach (by microinjection of foreign DNA into the pronuclei of fertilized zygotes, and then integrating the transgene sequences into random sites of the mouse genome with variable frequency), gene recombination system, and genetic modifications in somatic cells. However, the two most common ways to generate the GEMMs are to activate the oncogenes or inactivate the tumor suppressor genes (or both) in mice through conditional transgenic methods and gene-targeting approaches, such as knock-out and knock-in. Among them, gain-of-function studies usually use transgenes, conditional transgenes, and knock-in approaches, whereas gene knockout and conditional knockout methods are typically employed in loss-of-function studies.

Fig1 DNA constructs used to generate GEMMs.¹

Function of GEMMs

GEMM is very adequate for studying the relationship between genes and tumors. It has tremendous advantages in studying the genetic causes of the occurrence and development of tumors, the mechanism of immune evasion, and the pathogenesis of tumors. It can artificially introduce gene mutations and subsequently provide an ideal cancer model not only to discover the immune checkpoint in tumors but also to benefit the clinical diagnosis and the treatment of cancers. For example, a variety of oncogene-induced cancers were detected in mouse models in which the perforin-encoding gene was knocked out, such as lymphoma (driven by the deletion of Trp53), and mammary adenocarcinomas (driven by the Erbb2 transgene). Concerning checkpoint therapies, it has been reported that inactivation of Myc in transformed T cell acute lymphoblastic lymphoma leads to tumor regression, possibly as a result of down-regulation of checkpoint gene CD47 and PD-L1 expression and corresponding activation of T cell immunity.

Despite all the merits mentioned, it should be noted that relatively synchronous expression of oncogene and resulting abundant tumor-initiating cells in GEMMs do not resemble the natural carcinogenesis history in humans and may cause differences in antitumor responses. Moreover, there are significant differences existing between the human and mouse immune systems, and the lack of the human immune system and tumor immune microenvironment prevents conventional GEMMs from evaluating and screening preclinical antibodies targeting human checkpoint molecules. This issue could be tackled by humanizing individual targeted checkpoint molecules like CTLA-4 and PD-1.

Services at Creative Biolabs

As a worldwide company, Creative Biolabs has always been at the forefront of biological research. We have broad scientific expertise, as well as teams of experts who have long-term work in tumor immune checkpoints and drug development fields. If you are interested in the genetic engineering mouse model and tumor immune checkpoints. If you are looking for a reliable partner. Creative Biolabs will be your best choice. Our comprehensive services include but are not limited to:

• Custom Immune Checkpoint Protein Development
• Antibody Development for Immune Checkpoints
• Immune Checkpoint Targeted Peptide Development
• Immune Checkpoint Targeted Small Molecular Drug Development
• Biomarker Development for Immune Checkpoint Inhibitor (ICI)
• Immune Checkpoint Assays
• Preclinical Research on Immune Checkpoint Drugs

Please refer to our Services Overview for more information, and feel free to contact us anytime for technical assistance.

Reference

1. Politi, et al. "How genetically engineered mouse tumor models provide insights into human cancers." Journal of clinical oncology 29.16 (2011): 2273.

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