Generation and Application of PTEN Knockout Mice

PTEN (phosphatase and tensin homolog) is a key tumor suppressor gene that regulates cell growth, proliferation, and survival by antagonizing the PI3K/AKT signaling pathway. Loss of PTEN function leads to uncontrolled cell proliferation and is associated with a variety of cancers, including prostate, breast, and brain cancers. The PTEN knockout mouse model is a powerful model for studying tumorigenesis and other disease processes associated with PTEN deficiency.

1. Generation of PTEN knockout mouse models:

PTEN knockout mouse models are generated through gene targeting techniques such as homologous recombination or the newer CRISPR/Cas9 gene editing technology. The process involves deleting or inactivating the PTEN gene in mouse embryonic stem cells, which are then used to generate knockout mouse models. There are two main types of PTEN knockout mouse models:

(1) Global PTEN knockout mouse model: This model involves the complete loss of the PTEN gene in all tissues, which often leads to early embryonic lethality due to widespread cellular dysfunction and abnormal growth.

(2) Conditional PTEN knockout mouse model: Using the Cre-LoxP system, researchers can inactivate PTEN in specific tissues (such as liver, brain, or prostate) or at specific developmental stages. This approach allows the study of PTEN function in specific organs while avoiding early death.

2. Applications of PTEN knockout mouse models:

(1) Cancer research: PTEN knockout mouse models are very useful for studying cancer development, especially prostate cancer, breast cancer, and brain cancer. Loss of the PTEN gene in specific tissues triggers tumorigenesis, allowing researchers to study the occurrence, development, and metastasis of cancer.

(2) Metabolic disorders: PTEN gene deficiency affects the regulation of insulin signaling, and the use of PTEN knockout mouse models can be used to study type 2 diabetes and insulin resistance.

(3) Neurobiology: PTEN gene plays a role in brain development and synaptic function. Conditional PTEN knockout mouse models in neural tissues are associated with autism spectrum disorders and epilepsy, and are used to study neurodevelopmental disorders.

(4) Drug testing: These PTEN knockout mouse models can be widely used in preclinical trials to test drugs targeting the PI3K/AKT pathway, which will help develop treatments for cancer and metabolic diseases.

In summary, the PTEN knockout mouse model is essential for researchers to understand the role of the PTEN gene in tumorigenesis, metabolic regulation, and neurobiology. This gene knockout mouse model can also provide important insights into therapeutic interventions for related diseases.

?

References

[1] Yu-Ru Lee and Pier Paolo Pandolfi, Cold Spring Harbor Perspectives in Medicine 2020 (doi: 10.1101/cshperspect.a037283)

[2] Sen Liu et al., Frontiers in Molecular Bioscience 2021 (doi: 10.3389/fmolb.2021.696537)