Last updated: May 23, 2012
Background on Mouse as a Model Organism
Background on Mouse as a Model Organism
Over the past century, the mouse has developed into the premier mammalian model system for genetic research. Scientists from a wide range of biomedical fields have gravitated to the mouse because of its close genetic and physiological similarities to humans, as well as the ease with which its genome can be manipulated and analyzed.
Although yeasts, worms and flies are excellent models for studying the cell cycle and many developmental processes, mice are far better tools for probing the immune, endocrine, nervous, cardiovascular, skeletal and other complex physiological systems that mammals share. Like humans and many other mammals, mice naturally develop diseases that affect these systems, including cancer, atherosclerosis, hypertension, diabetes, osteoporosis and glaucoma. In addition, certain diseases that afflict humans but normally do not strike mice, such as cystic fibrosis and Alzheimer's, can be induced by manipulating the mouse genome and environment. Adding to the mouse's appeal as a model for biomedical research is the animal's relatively low cost of maintenance and its ability to quickly multiply, reproducing as often as every nine weeks.
Mouse models currently available for genetic research include thousands of unique inbred strains and genetically engineered mutants. There are mice prone to different cancers, diabetes, obesity, blindness, Lou Gehrig's disease, Huntington's disease, anxiety, aggressive behavior, alcoholism and even drug addiction. Immunodeficient mice can also be used as hosts to grow both normal and diseased human tissue, a boon for cancer and AIDS research.
In the early days of biomedical research, scientists developed mouse models by selecting and breeding mice to produce offspring with the desired traits. Researchers also learned to produce useful, new models of genetic disease quickly and in large numbers by exposing mice to DNA-damaging chemicals, a process known as chemical mutagenesis.
In recent decades, researchers have utilized an array of innovative genetic technologies to produce custom-made mouse models for a wide array of specific diseases, as well as to study the function of targeted genes. One of the most important advances has been the ability to create transgenic mice, in which a new gene is inserted into the animal's germline. Even more powerful approaches, dependent on homologous recombination, have permitted the development of tools to "knock out" genes, which involves replacing existing genes with altered versions; or to "knock in" genes, which involves altering a mouse gene in its natural location. To preserve these extremely valuable strains of mice and to assist in the propagation of strains with poor reproduction, researchers have taken advantage of state-of-the-art reproductive technologies, including cryopreservation of embryos, in vitro fertilization and ovary transplantation.
The Jackson Laboratory, a publicly supported national repository for mouse models in Bar Harbor, Maine, has played a crucial role in the development of the mouse into the leading model for biomedical research. Established in 1929, the non-profit center pioneered the use of inbred laboratory mice to uncover the genetic basis of human development and disease. In fact, the famous "Black 6" or C57BL/6J mouse strain whose genome is the focus of the landmark sequencing effort was developed in the early 1920s by The Jackson Laboratory founder Clarence Cook Little.
Today, researchers at The Jackson Laboratory pursue projects in areas that include cancer, development and aging, immune system and blood disorders, neurological and sensory disorders, and metabolic diseases. Informatics researchers work with the public sequencing consortium to curate and integrate the sequenced mouse genome data with the wealth of biological knowledge collected in Jackson's Mouse Genome Informatics resource.
In addition, The Jackson Laboratory distributes 2,700 different strains and stocks as breeding mice, frozen embryos or DNA samples. In FY 2002 alone, the lab supplied approximately 2 million mice to the international scientific community.
Listed below is a sampling of mouse models developed and/or distributed by The Jackson Laboratory, along with brief descriptions of the human diseases they are helping scientists to understand:
- Down Syndrome - One of the most common genetic birth defects in humans, occurring once in every 800 to 1,000 live births, Down syndrome results from an extra copy of chromosome 21, an abnormality known as trisomy. The Ts65Dn mouse, developed at The Jackson Laboratory, mimics trisomy 21 and exhibits many of the behavioral, learning, and physiological defects associated with the syndrome in humans, including mental deficits, small size, obesity, hydrocephalus and thymic defects. This model represents the latest and best improvement of Down syndrome models to facilitate research into the human condition.
- Cystic Fibrosis (CF) - The Cftr knockout mouse has helped advance research into cystic fibrosis, the most common fatal genetic disease in the United States today, occurring in approximately one of every 3,300 live births. Scientists now know that CF is caused by a small defect in the gene that manufactures CFTR, a protein that regulates the passage of salts and water in and out of cells. Studies with the Cftr knockout have shown that the disease results from a failure to clear certain bacteria from the lung, which leads to mucus retention and subsequent lung disease. These mice have become models for developing new approaches to correct the CF defect and cure the disease.
- Cancer - The p53 knockout mouse has a disabled Trp53 tumor suppressor gene that makes it highly susceptible to various cancers, including lymphomas and osteosarcomas. The mouse has emerged as an important model for human Li-Fraumeni syndrome, a form of familial breast cancer.
- Glaucoma - The DBA/2J mouse exhibits many of the symptoms that are often associated with human glaucoma, including elevated intraocular pressure. Glaucoma is a debilitating eye disease that is the second leading cause of blindness in the United States.
- Type 1 Diabetes - This autoimmune disease, also known as Juvenile Diabetes, or Insulin Dependent Diabetes Mellitus (IDDM), accounts for up to 10 percent of diabetes cases. Non-obese Diabetic (NOD) mice are enabling researchers to identify IDDM susceptibility genes and disease mechanisms.
- Type 2 Diabetes - A metabolic disorder also called Non-Insulin Dependent Diabetes Mellitus (NIDDM), this is the most common form of diabetes and occurs primarily after age 40. The leading mouse models for NIDDM and obesity research were all developed at The Jackson Laboratory: Cpefat, Lepob, Leprdb and tub.
- Epilepsy - The "slow-wave epilepsy," or swe, mouse is the only model to exhibit both of the two major forms of epilepsy: petit mal (absence) and grand mal (convulsive). It shows particular promise for research into absence seizures, which occur most often in children.
- Heart Disease - Elevated blood cholesterol levels and plaque buildup in arteries within three months of birth (even on a low-fat diet) are characteristics of several experimental models for human atherosclerosis: the Apoe knockout mouse and C57BL/6J.
- Muscular Dystrophy - The Dmd mdx mouse is a model for Duchenne Muscular Dystrophy, a rare neuromuscular disorder in young males that is inherited as an X-linked recessive trait and results in progressive muscle degeneration.
- Ovarian Tumors - The SWR and SWXJ mouse models provide excellent research platforms for studying the genetic basis of ovarian granulosa cell tumors, a common and very serious form of malignant ovarian tumor in young girls and post-menopausal women.
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