MOUSE AS A MODEL IN BIOPHARMACEUTICAL RESEARCH

Ø  For studying the cell cycle and many development processes – it is well established that yeasts, worms and flies as excellent model organisms.

Ø  Mouse is genetically closely related to humans.  Another reason for mouse’s appeal as a model for biomedical research is due to its low cost of maintenance and its ability to quickly multiply reproducing as often as every nine weeks.

Ø  Due to close genetic and physiological similarities of mouse to humans, mice are far better tools for probing the immune, endocrine, nervous, cardiovascular, skeletal and other physiological systems.

Ø  It should be noted that similar to humans and many other mammals, mice naturally develop diseases including cancer, atherosclerosis, hypertension, diabetes, osteoporosis and glaucoma.

Ø  Interestingly, certain disease that doesn’t afflict mice but are normal in humans can be nicely induced into mice by manipulating its genome.

Nude mouse:

o   A nude mouse (is a mutant mouse) is a laboratory mouse with an inhibited immune system.   These are also called athymic nude mouse – due to the fact that these models lack normal thymus gland and has a defective immune system because of a genetic mutation. That means intrinsic safety mechanism is now turned off.

o   The mouse lacks body hair, which gives it the "nude" nickname.

o   The nude mouse is valuable to research because it can receive many different types of tissue and tumor grafts, as it mounts no rejection response.

Knockout mouse:

v  A knockout mouse is a genetically modified mouse in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA.

v  Knocking out the activity of a gene provides information about what that gene normally does. Humans share many genes with mice. Consequently, observing the characteristics of knockout mice gives researchers information that can be used to better understand how a similar gene may cause or contribute to disease in humans.

v  There are several thousand different strains of knockout mice.  Many mouse models are named after the gene that has been inactivated.

There is a relatively high number of strains and substrains of natural immunodeficiency models and gene deficient transgenic models available for genetic and immunological studies. The strains have specific deficiencies in MHC class I, II or both; B cell or T cell defects, or defects in both, as well as immunodeficiency due to knockdown of genes for cytokines, cytokine receptors, TLR receptors and a variety of transducers and transcription factors of signaling pathways. The use of these inbred strains has contributed to identifying hundreds of genes responsible for controlling the outcome of microbial infections and to understanding fundamental questions in the molecular control of immune deficiency or autoimmunity. [Immunodeficient Mouse Models: An Overview, The Open Immunology Journal, 2009, 2, 79-85]