Two major inbred strains of immuno-deficient mice are used to study the immune system and transplantation. These are nude mice, and SCID mice.
A nude mouse is an inbred strain whose thymus gland is missing or damaged, resulting in a deficient immune system. They have a very small number of T-lymphocytes, which are essential to the immune response. These mice are called “nude” because they also lack fur. With a very limited immune system, the nude mouse is able to receive many tissue and tumor grafts from many different species without suffering a rejection response. They are often used to grow grafted tissue, and are used in research to test new methods of imaging and treating tumors.
Nude mice were first discovered by Dr. N. R. Grist in 1962 at the virus laboratory at Ruchill hospital, Glasgow. They are pink-skinned and hairless, with oversized ears. Without a thymus gland, these mice are unable to kill virus infected or malignant cells, form most antibodies, reject tissue grafts or develop hypersensitivity responses – all of which require T-lymphocytes. The adaptive immune response of nude mice is so limited that they are even able to accept grafted tissue from other species. This makes them a vital model for cancer research, as they allow the study of human tumors, which retain their original characteristics.
Rosalyn Yalow realized that nude mice could be created using a radioimmunoassay techniques to remove the gene required for the thymus growth factor hormone. She was awarded the Nobel Prize in medicine for this discovery in 1977. An alternative method of creating nude mice is to remove the thymus from the mouse completely within 24 hours of birth. Nude mice are usually bred from the inbred strain, rather than created artificially by either of these methods.
In the early 1970s researchers saw the advantages that this model had to offer, but because their immune response was badly compromised, nude mice were prone to infections and often died before experiments were completed. Using sterile techniques to handle the mice, John Stehlin and Beppino Giovanella at the Stehiln Foundation for Caner Research, were the first researchers to keep nude mice alive for two years. In this time they were able to successfully grow and study human tumors.
Nude mice have allowed many insights into the immune system, leukemia, solid tumors, AIDS and other forms of immune deficiency.