Molecules like green fluorescence protein (GFP) and luciferase are much used for tumours inside mouse models. Engineered into tumour cells, these light-emitting markers can be detected by a camera and allow tumour progress to be tracked and quantified.
The downside is that these markers are recognized as foreign, so the immune system must often be turned off in mouse models.
Now “glowing head” mice promise to be better models in cancer research, immunology and tissue transplants, a recent paper reports. They work by tricking the immune system into accepting light-emitting molecules.
“The mouse immune system recognizes GFP and luciferase as foreign molecules - originated from jellyfish and firefly, respectively - and responds appropriately,” notes Chi-Ping Day and Glenn Merlino, first and senior author of the study in PLOS ONE and researcher at the NIH’s National Cancer Institute in Bethesda, Maryland. “We realized then that the ultimate solution to this issue was to create a mouse innately expressing GFP and luciferase.”
Genetic modification
The immune system sees these proteins as “self” molecules and tolerates them when transplanted.
The technique involves an embryo having GFP or luciferase genes inserted into its genome and so being born without immune cells against these marker proteins, which are viewed then as “self” molecules.
The group found that cancer models based on the glowing head mouse allow consistent monitoring of disease in the presence of a functioning immune system. Therefore, such models should prove to be superior at mimicking clinical trials and predicting clinical outcome.
The antigenicity of the optical reporter resulted in a 5-fold decrease in tumor growth in wild type mice as compared to glowing head mice.
Before this paper, researchers in the US and other countries who learned about the mice from the NIH Invention Report and meetings contacted the team to request glowing head mice. “So far we have sent the mice to nearly 20 researchers,” says Day.
Many want to use them to build cancer models with normal immunity. Others to track stem cells or tissue repair in normal mice. “We are in the process of depositing the glowing head mice in to the Jackson Laboratory, which will further facilitate their distribution to the research community,” adds Day.
The researchers found that even the slightest immunity against tumor antigens can significantly change the results of cancer progression and treatment. This means that immunity is critical for predicting drug efficacy.
“Therefore, caution should be taken when attempting to interpret drug efficacy data from studies using mice lacking a normal immune system, which are widely used in current preclinical studies,” advises Day.
The antigenicity of the optical reporter resulted in a 5-fold decrease in tumor growth in wild type mice as compared to glowing head mice.
After surgical removal of primary tumors, metastasis developed resulting in the death of the mice. Metastasis was significantly delayed in the wild type mice as compared to the “glowing head” mice, so the former lived about twice as long as the new mice. This is because the immune system of wild type mice recognizes and attacks the optical marker molecules.
Source: PLOS One
“Glowing Head” Mice: A Genetic Tool Enabling Reliable Preclinical Image-Based Evaluation of Cancers in Immunocompetent Allografts."
Chi-Ping Day et al
DOI: 10.1371/journal.pone.0109956