Genetically modified mouse
Encyclopedia
A genetically modified mouse is a mouse
that has had its genome
altered through the use of genetic engineering
techniques. Genetically modified mice are commonly used for research or as animal models of human diseases.
created the first genetically modified animal by inserting a DNA virus into an early-stage mouse embryo
and showing that the inserted genes were present in every cell. However the mice did not pass the transgene
onto their offspring. In 1981 the laboratories of Frank Ruddle from Yale
and Frank Constantini and Elizabeth Lacy in Oxford
injected purified DNA into a single-cell mouse embryo and showed transmission of the genetic material to subsequent generations. During the early eighties the technology used to generate genetically modified mice was improved into a tractable and reproducible method.
injection into a single cell of the mouse embryo, where it will randomly integrate into the mouse genome. This method creates a transgenic mouse and is used to insert new genetic information into the mouse genome or to over-express endogenous
genes. The second approach involves modifying embryonic stem cells with a DNA construct
containing DNA sequences homologous to the target gene. Embyonic stem cells that recombine
with the genomic DNA are selected for and they are then injected into the mice blastocysts. This method is used to manipulate a single gene, in most cases "knocking out"
the target gene, although more subtle genetic manipulation can occur (e.g. only changing single nucleotides).
, where the activity of a single (or in some cases multiple) genes are removed. They have been used to study and model obesity, heart disease, diabetes, arthritis, substance abuse, anxiety, aging and Parkinson disease. Transgenic mice generated to carry cloned oncogenes and knockout mice lacking tumor suppressing genes
have provided good models for human cancer
. Hundreds of these oncomice
have been developed covering a wide range of cancers affecting most organs of the body and they are being refined to become more representative of human cancer. The disease symptoms and potential drugs or treatments can be tested against these mouse models.
A mouse has been genetically engineered to have increased muscle growth and strength by overexpressing the insulin-like growth factor I (IGF-I) in differentiated muscle fibers. Another mouse has had a gene altered that is involved in glucose metabolism and runs faster, lives longer, is more sexually active and eats more without getting fat than the average mouse (see Metabolic supermice
).
House mouse
The house mouse is a small rodent, a mouse, one of the most numerous species of the genus Mus.As a wild animal the house mouse mainly lives associated with humans, causing damage to crops and stored food....
that has had its genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
altered through the use of genetic engineering
Genetic engineering
Genetic engineering, also called genetic modification, is the direct human manipulation of an organism's genome using modern DNA technology. It involves the introduction of foreign DNA or synthetic genes into the organism of interest...
techniques. Genetically modified mice are commonly used for research or as animal models of human diseases.
History
In 1974 Rudolf JaenischRudolf Jaenisch
Rudolf Jaenisch is a biologist at MIT. He is a pioneer of transgenic science, in which an animal’s genetic makeup is altered. Jaenisch has focused on creating transgenic mice to study cancer and neurological diseases....
created the first genetically modified animal by inserting a DNA virus into an early-stage mouse embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...
and showing that the inserted genes were present in every cell. However the mice did not pass the transgene
Transgene
A transgene is a gene or genetic material that has been transferred naturally or by any of a number of genetic engineering techniques from one organism to another....
onto their offspring. In 1981 the laboratories of Frank Ruddle from Yale
YALE
RapidMiner, formerly YALE , is an environment for machine learning, data mining, text mining, predictive analytics, and business analytics. It is used for research, education, training, rapid prototyping, application development, and industrial applications...
and Frank Constantini and Elizabeth Lacy in Oxford
University of Oxford
The University of Oxford is a university located in Oxford, United Kingdom. It is the second-oldest surviving university in the world and the oldest in the English-speaking world. Although its exact date of foundation is unclear, there is evidence of teaching as far back as 1096...
injected purified DNA into a single-cell mouse embryo and showed transmission of the genetic material to subsequent generations. During the early eighties the technology used to generate genetically modified mice was improved into a tractable and reproducible method.
Methods
There are two basic technical approaches to produce genetically modified mice. The first involves pronuclearCell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
injection into a single cell of the mouse embryo, where it will randomly integrate into the mouse genome. This method creates a transgenic mouse and is used to insert new genetic information into the mouse genome or to over-express endogenous
Endogenous
Endogenous substances are those that originate from within an organism, tissue, or cell. Endogenous retroviruses are caused by ancient infections of germ cells in humans, mammals and other vertebrates...
genes. The second approach involves modifying embryonic stem cells with a DNA construct
DNA construct
A DNA construct is an artificially constructed segment of nucleic acid that is going to be "transplanted" into a target tissue or cell...
containing DNA sequences homologous to the target gene. Embyonic stem cells that recombine
Genetic recombination
Genetic recombination is a process by which a molecule of nucleic acid is broken and then joined to a different one. Recombination can occur between similar molecules of DNA, as in homologous recombination, or dissimilar molecules, as in non-homologous end joining. Recombination is a common method...
with the genomic DNA are selected for and they are then injected into the mice blastocysts. This method is used to manipulate a single gene, in most cases "knocking out"
Gene knockout
A gene knockout is a genetic technique in which one of an organism's genes is made inoperative . Also known as knockout organisms or simply knockouts, they are used in learning about a gene that has been sequenced, but which has an unknown or incompletely known function...
the target gene, although more subtle genetic manipulation can occur (e.g. only changing single nucleotides).
Uses
Genetically modified mice are used extensively in research as models of human disease. The most common type is the knockout mouseKnockout mouse
A knockout mouse is a genetically engineered mouse in which researchers have inactivated, or "knocked out," an existing gene by replacing it or disrupting it with an artificial piece of DNA...
, where the activity of a single (or in some cases multiple) genes are removed. They have been used to study and model obesity, heart disease, diabetes, arthritis, substance abuse, anxiety, aging and Parkinson disease. Transgenic mice generated to carry cloned oncogenes and knockout mice lacking tumor suppressing genes
Tumor suppressor gene
A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from one step on the path to cancer. When this gene is mutated to cause a loss or reduction in its function, the cell can progress to cancer, usually in combination with other genetic changes.-Two-hit hypothesis:Unlike...
have provided good models for human cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
. Hundreds of these oncomice
Oncomouse
The OncoMouse or Harvard mouse is a type of laboratory mouse that has been genetically modified using modifications designed by Philip Leder and Timothy A Stewart of Harvard University to carry a specific gene called an activated oncogene. The activated oncogene significantly increases the mouse’s...
have been developed covering a wide range of cancers affecting most organs of the body and they are being refined to become more representative of human cancer. The disease symptoms and potential drugs or treatments can be tested against these mouse models.
A mouse has been genetically engineered to have increased muscle growth and strength by overexpressing the insulin-like growth factor I (IGF-I) in differentiated muscle fibers. Another mouse has had a gene altered that is involved in glucose metabolism and runs faster, lives longer, is more sexually active and eats more without getting fat than the average mouse (see Metabolic supermice
Metabolic supermice
Metabolic supermice are mice which as a result of genetic modification have up to 100 times the concentration of the PEPCK-C enzyme in their muscles, compared to ordinary mice....
).