Knock-out Model Development Service
In the field of biomedical research, knock-out mouse models have emerged as invaluable tools for studying gene function and understanding the mechanisms underlying various diseases. Developed through genetic modification techniques, knock-out models involve the targeted deletion or inactivation of specific genes. Our company has been at the forefront of utilizing knock-out models to drive groundbreaking research and develop cutting-edge solutions for rare diseases.
What is a Knock-out Model?
A knock-out model refers to an animal model, typically a mouse, in which a specific gene has been intentionally disrupted or rendered non-functional. This genetic modification allows researchers to investigate the consequences of gene loss on various physiological processes, disease development, and behavior. By selectively targeting and inactivating genes of interest, knock-out models enable scientists to gain critical insights into gene function and its impact on human health.
Fig.1 Construction of SELECTIV mice overexpressing AV receptor (Aavr). (Zengel, James, et al., 2023)The creation of knock-out models involves meticulous genetic engineering techniques. Traditional methods employ homologous recombination to replace or disrupt specific genes with a non-functional sequence. More recently, advanced technologies like CRISPR/Cas9 have revolutionized the field by providing precise and efficient gene editing capabilities.
Knock-out Models for Rare Diseases
By comparing the knock-out animal models to their wild-type counterparts, researchers can elucidate the specific contributions of a gene to various biological processes. For instance, studying the knock-out of a gene involved in a rare disease can provide invaluable insights into the underlying mechanisms and potential therapeutic targets. By selectively targeting genes implicated in rare diseases and generating corresponding knock-out models, researchers can mirror the disease phenotype in mice. This approach allows for a comprehensive investigation of disease progression, pathogenesis, and potential therapeutic interventions.
Table 1 Knock-out models as a resource for rare diseases. (da Silva-Buttkus, P., et al., 2023)
| Grouping | Gene | Rare disease | GMC KO mouse model phenotypes: new findings |
|---|---|---|---|
| Known RD genes | Nacc1 | Neurodevelopmental disorder with epilepsy, cataracts, feeding difficulties, and delayed brain myelination (het) | Viable mice after weaning, renal |
| Bach2 | Chronic myeloid leukemia | Failure to thrive, eye | |
| Klotho alpha | Familial hyperphosphatemic tumoral calcinosis | Histological evidence of diverse tissue calcifications | |
| Known RD genes with no pre-existing KO mouse models | Kansl1l | Koolen-de vries syndrome | Viable mice**, in-depth eye |
| Acsf3 | Combined malonic and methylmalonic aciduria | Renal, Immuno | |
| Pcdhgb2 | Prune belly syndrome | Viable mice, anemia, cardio | |
| Rabgap1 | Warburg micro syndrome 1 | Histological evidence of decreased corpus callosum | |
| Cox7a2 | Fatal infantile cardioencephalomyopathy due to cytochrome C oxidase deficiency | Growth failure, histological evidence of altered brown adipocytes | |
| Previously unreported RD gene candidates: Novel mouse models (potential new gene targets) | Zdhhc5 | No associated RD | Dysmorphology, eye |
| Wsb2 | No associated RD | Dysmorphology, eye, renal, heart, male infertility |
Our Services
The utilization of knock-out models in rare diseases extends beyond understanding disease mechanisms to facilitate drug discovery and therapeutic development. These models serve as invaluable tools for preclinical studies, allowing researchers to conduct drug safety evaluation and pharmacokinetics studies. By testing various compounds or rare disease therapies in knock-out models, our company has been able to identify promising candidates for further development, accelerating research into rare disease drugs and therapies.
- Animal Species for Model Development
-Mouse
-Rat
-Rabbit-Pig
-Dog-Monkey
-Cat-Zebrafish
-Others - Methods of Knock-out Model Development
-Homologous Recombination
-CRISPR-based Gene Editing - Types of Knock-out Model Development
Constitutive / Conventional / Whole-body Knock-out Models:
Knock out the target gene according to your requirements, so that its function is permanently lost in all cells of the mouse and throughout its life.
KO First (Conditional Ready) Models:
Achieve more precise gene knockout and conduct more targeted research by time- or tissue-specific knockout of your target genes of interest.
Conditional (Tissue-specific or Inducible) Knock-out Models:
Enable the generation of both reporter gene knock-in model and conditional knock-out models simultaneously from a single project by utilizing either Cre/LoxP recombination system or Flp/FRT recombination system.
RNAi Knock-down Models:
We often employ conditional and/or inducible methods in combination with RNA interference to reduce the expression of the target gene.
Why Choose Us?
With many years of experience and a proven track record of quality, innovation, and customer support, our company provides comprehensive services for leading and emerging biopharmaceutical companies and scientific research institutions to develop knock-out models for rare diseases. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Zengel, James, et al. "Hardwiring tissue-specific AAV transduction in mice through engineered receptor expression." Nature Methods (2023): 1-12.
- da Silva-Buttkus, P., et al. "knock-out mouse models as a resource for the study of rare diseases." Mammalian Genome (2023): 1-18.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.