Genetically Engineered Animal Models (GEMs) or Genetically Engineered Mouse Models (GEMMs) are of vital importance in modern cancer research. With Protheragen's GEM development services, we aim to enable the further advances in oncology innovation. Using our unique technologies, extensive knowledge, and adaptable systems, we offer researchers and pharmaceutical partners all the requisite resources to untangle the complexities of cancer biology and expedite the therapeutic development process.
Overview of Genetically Engineered Models (GEMs)
Genetically Engineered Animal Models (GEMs) are highly specialized organisms created by inserting, deleting, or modifying specific genes to emulate human diseases, especially cancers. Understanding the pathways of tumor initiation, progression, metastasis, and therapy resistance would be impossible without these models. Through GEMs, researchers can replicate multifaceted human cancer genotypes within a living organism.
Fig.1 Advantages and tools of murine models to study tumor evolution. (Hill W.,
et al., 2021)
The foundation of GEMs lies in the manipulation of the animal genome—most commonly in mice—using advanced technologies such as:
- CRISPR/Cas9-mediated gene editing
- Cre-LoxP conditional recombination
- Homologous recombination in embryonic stem cells
- RNA-guided base editing and prime editing
These methods enable the expression of gain-of-function, loss-of-function, and conditional alleles allowing precise control over the temporal and spatial activation of genetic modifications. In cancer research, GEMs act as translational platforms that connect in vitro research to clinical trials.
Current Status of Genetically Engineered Model (GEM) Development
Recent years have seen significant progress in GEM development due to new technologies and a better understanding of the biology of cancer. The global availability of GEMs owing to reduction of time and cost with the adoption of CRISPR-Cas9 technology is a boon to researchers all over the world. Moreover, advanced imaging and high-throughput sequencing have improved GEM characterization, providing enormous data sets to analyze.
Table 1. Genetically engineered mouse models for cancer. (Biswas K., et al., 2023)
| Disease |
Gene |
Allele |
Type of model |
Exons or domain affected |
Cre and target tissue |
MSI |
Phenotype |
| Lynch Syndrome |
Msh2 |
Msh2 loxp |
Conditional |
Exon 12 |
Villin-Cre; intestine |
Yes |
Small intestinal tumor, reduced lifespan (12 mo) |
| Msh2 |
Msh2 loxp |
Conditional |
Exon 12 |
Ella-Cre; all tissues |
Yes |
Lymphoma, GI adenosarcoma, reduced lifespan (6 mo) |
| Mlh1 |
Mlh1 flox |
Conditional |
Exon 4 |
Ella-Cre; all tissues |
Yes |
Lymphoma, intestinal and skin tumor, reduced lifespan (12 mo) |
| Mlh1 |
Mlh1 G67R |
Knock-in |
ATP-binding domain |
NA |
Yes |
Lymphoma, intestinal and skin tumor, reduced lifespan (12 mo), infertile |
| Msh6 |
Msh6 T1217D |
Knock-in |
Msh2-Msh6 heterodimer interface |
NA |
No |
Lymphoma, endometrial cancer, reduced lifespan (12 mo) |
| Msh6 |
Msh6 − |
Knockout |
3′ of exon 4 |
NA |
No |
Lymphoma, endometrial cancer, reduced lifespan (12 mo) |
| Pms2 |
Pms2 E702K |
Knock-in |
Endonuclease domain |
NA |
Yes |
Lymphoma |
| Hereditary Breast and Ovarian Cancer (HBOC) |
Brca1 |
Brca1 Δ11 |
Conditional |
Exon 11 |
EIIa-Cre; All tissues |
NA |
Survive in p53+/−or p53−/− background, develop mammary tumor in 6-10 mo |
| Brca1 |
Brca1 Δ11 |
Conditional |
Exon 11 |
Wap-Cre; mammary gland |
NA |
Develop mammary tumor with long latency (10-13 mo) |
| Brca1 |
Brca1 S1598F |
Knock-in |
BRCT domain, disrupts phospho-protein recognition domain |
NA |
NA |
Increased tumor incidence when combined with p53 mutation, males are sterile |
| Brca2 |
Brca2 Δ11 |
Conditional |
Exon 11 containing BRC repeats (RAD51-binding motifs) |
K14-Cre; epithelial cells |
NA |
Development of mammary and skin tumors, reduced latency (181 d) in p53fl/fl background |
| Brca2 |
Brca2 G25R |
Knock-in |
PALB2 interaction domain |
NA |
NA |
B-cell lymphoma and other tumors with long latency, increased tumor prevalence in p53 mutant background |
| Palb2 |
Palb2 Δ2–3 |
Conditional |
Exons 2 and 3 |
K14-Cre; epithelial cells |
NA |
Mammary and skin tumors, latency reduced (192 d) in p53fl/fl background |
| Palb2 |
Palb2 CC6/CC6 |
Knock-in |
Amino acids 24-26 (LKK to AAA) |
|
NA |
Reduced male fertility, no gross developmental defect, MMC sensitivity |
Our Services
From target identification to in vivo validation, Protheragen offers comprehensive support for cancer researchers. Our team of molecular biologists, immunologists, and veterinary scientists ensures each model is biologically relevant and technically robust.
Types of Genetically Engineered Models (GEMs)
- Germline Knockout and Knock-in Models
Engineered to introduce or disrupt genes globally, ideal for hereditary cancer studies such as BRCA1-, APC-, or TP53-associated syndromes. These models offer foundational insight into tumorigenesis and are routinely used in target validation and biomarker discovery.
- Conditional Knockout Models
Employing Cre-LoxP technology, Protheragen generates tissue-specific and temporally controlled deletions. For example, Pdx1-Cre; LSL-KrasG12D; Trp53loxP/loxP mice mimic spontaneous pancreatic cancer, enabling precise drug response assessment.
- Inducible Expression Models
Using tetracycline- or tamoxifen-regulated systems, these models activate or silence gene expression postnatally, facilitating studies of gene function during tumor progression and post-treatment relapse.
- Humanized Immune System Models
Immunodeficient GEMs engrafted with human hematopoietic stem cells and tumors. These are essential for testing T-cell therapies, checkpoint inhibitors, and vaccine candidates in an immunologically human context.
- Neoantigen-Expressing Models
Developed to express tumor-specific antigens under endogenous or inducible promoters, these models enable immunogenicity profiling, immune escape analysis, and therapeutic vaccine development.
- CIN and WGD Models
GEMs engineered to model chromosomal instability (CIN) or whole-genome duplication (WGD) events. Used to investigate mechanisms of drug resistance, clonal selection, and recurrence in aggressive cancers.
Optional Disease Models and Modifiable Gene
| Disease Name (Model) |
Modifiable Gene(s) |
Species |
| Lung adenocarcinoma |
KRAS, TP53, LKB1 (STK11) |
Mouse |
| Pancreatic ductal adenocarcinoma (PDAC) |
KRAS, TP53, UCP2 |
Mouse |
| Breast cancer |
PyMT (polyoma middle-T), HER2, TP53 |
Mouse |
| Colorectal cancer |
APC, KRAS, EGFR |
Mouse |
| Glioblastoma |
TP53, PTEN, EGFR |
Mouse |
| Prostate cancer |
PTEN, TP53 |
Mouse |
| Melanoma |
BRAF (V600E) |
Mouse |
| HPV-related cervical cancer |
HPV E6/E7 |
Mouse |
| Disease Name (Model) |
Modifiable Gene(s) |
Species |
| Humanized immune system tumor |
PD-1, PD-L1, CTLA-4 |
Mouse |
| Osteosarcoma (spontaneous) |
GSTP1, MDR1, FLT3 |
Dog |
End-to-End GEM Development Workflow
Consultation
Scientific consultation to design optimal model architecture based on study objectives, ensuring alignment with the specific research goals and desired outcomes.
Vector Design
CRISPR/Cas9 or Cre-Lox targeting vectors tailored to gene locus and regulatory elements, with careful consideration of the most effective delivery system for the target organism.
Genome Editing
Embryonic stem cell manipulation or zygote microinjection for gene modification, followed by rigorous validation to ensure precision and efficiency in the modification process.
Founder Validation
Genotyping, sequencing, and functional assays to confirm correct targeting, with the added step of confirming germline transmission and stability of the modification.
Colony Expansion
Breeding strategy development and generation of experimental cohorts, while monitoring the health and genetic integrity of the colony over successive generations.
Phenotypic Analysis
Tumor growth monitoring, histopathology, immune profiling, and drug response testing, complemented by detailed analysis of the observed phenotypic changes to understand disease progression.
Whether modeling BRCA-deficient breast cancer or MSI-high colorectal tumors, Protheragen remains committed to delivering world-class GEM solutions that meet the demands of precision oncology. If you are interested in our services, please feel free to contact us.
References
- Hill, William, Deborah R. Caswell, and Charles Swanton. "Capturing cancer evolution using genetically engineered mouse models (GEMMs)." Trends in cell biology 31.12 (2021): 1007-1018.
- Biswas, Kajal, et al. "Genetically engineered mouse models for hereditary cancer syndromes." Cancer Science 114.5 (2023): 1800-1815.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
