Korc Poster Final 11 23 10
•Download as PPTX, PDF•
0 likes•155 views
Knockout Rat Consortium (KORC)
![The Knockout Rat Consortium (KORC) Aron M. Geurts1, 2, 3, Edwin Cuppen4, 5, and Eric M. Ostertag6, 7, 81Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI, USA. 2PhysGen Knockout Team, Human and Molecular Genetics Center, Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA. 3Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA. 4Hubrecht Institute, Developmental Biology and Stem Cell Research, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht, Utrecht, Netherlands. 5Department of Medical Genetics, University Medical Center Utrecht, Utrecht, Netherlands. 6Department of Microbiology, Immunology, and Molecular Genetics, University of Kentucky, Lexington, KY, USA. 7 Department of Pathology & Laboratory Medicine, University of Kentucky Chandler Hospital, Lexington, KY, USA. 8Transposagen Biopharmaceuticals, Inc., Lexington, KY, USA. Summary ENU-Mediated Mutagenesis The Knockout Rat Consortium (KORC) is formed by individuals and institutions interested in the goal of creating knockout rats using multiple technologies including transposon-based and chemical mutagenesis. The KORC website is www.knockoutrat.organd contains a database, news items, a discussion form, and links that are useful to researchers interested in rat models. The KORC database lists the majority of knockout rats that are currently available to the research community and can be searched by gene name, ontology, or disease association. The KORC now has over 300 genetically modified rats in its database. Examples of knockout rats available include a SCID model, a p53 knockout, a model of pain (Trpc4), a model of hydrocephalus (Myo9a), and a new model of obesity (Mc4r). The SCID rat contains an insertional mutation within the adenosine deaminase (Ada) gene, which is an underlying cause of many cases of severe combined immunodeficiency (SCID) in humans. SCID rats share similar or identical defects reported in mice and humans with Ada mutations (e.g., athymia, depressed cell counts in the spleen, and severe liver defects). The SCID rat can be used for the transplantation of stem cell populations to create humanized tissues or organs for in vivo analysis. The world’s first p53 knockout rat is also available (orders fulfilled by Charles River Laboratories) and now has extensive phenotype information, including tumor spectrum data. p53 knockout rats display a wide variety of solid tumors, such as rhabdomyosarcoma, hemangiosarcoma, adrenocortical carcinoma and others. The Trpc4 knockout rat is a novel model for pain research and demonstrates greatly reduced sensitivity to visceral pain. A rat knockout of Myo9a enables researchers to study hydrocephalus in an animal model that allows facile surgical manipulation. Melanocortin 4 receptor (Mc4r) mutations are the single most common form of monogenic obesity in humans. The Mc4r knockout rat is obese and gains white adipose tissue rapidly due to hyperphagia. On behalf of the KORC we invite all interested investigators to participate in our efforts to assemble a repository of knockout rats. This will be a tremendous resource for the rat research community. N-ethyl-N-nitrosourea(ENU) transfers its ethyl group to oxygen or nitrogen radicals present on the DNA. Subsequent replication of damaged DNA can result in mispairing and produce single base substitutions. To generate mutant rats, males are treated with ENU to cause alkylation of DNA followed by point mutations in rapidly dividing spermatogonial stem cells. Every affected cell will contain a random and unique set of induced mutations. Thus, one treated male will have a genetically heterogeneous sperm population contributing to offspring with distinct mutations. Offspring from a treated male and wildtype female will result progeny that are screened for heterozygous mutations identified using high-throughput mutation discovery methods. Mutants of interest can then be bred to homozygosity. Advantages of ENU mutagenesis include a very high frequency of mutation and the ability to create hypomorphic mutations. Trpc4 Name: Transient receptor potential cation channel, subfamily C, member 4 Symbol: Trpc4 Genetic Map: Mutation DNA transposon gene trap insertion within intron 1 Associated Human Diseases: ,[object Object]](https://image.slidesharecdn.com/korcposterfinal112310-12923736054757-phpapp02/85/Korc-Poster-Final-11-23-10-1-320.jpg)
Recommended
Recommended
More Related Content
What's hot
What's hot (20)
Similar to Korc Poster Final 11 23 10
Similar to Korc Poster Final 11 23 10 (20)
Korc Poster Final 11 23 10
- 9. Our goal is to generate at least one rat with a null mutation for every gene in the rat genome.
- 13. Carcinogenicity and toxicology studies
- 14. Aging, antioxidant, inflammatory, and insulin resistance studiesContact information On behalf of the KORC we invite all interested investigators to participate in our efforts to assemble a repository of knockout rats. This will be a tremendous resource for the rat research community. For more information or to browse our current list of knockout models, please visit the KORC website at www.knockoutrat.org. If you wish to initiate your own project of rat mutagenesis please contact KORC at info@knockoutrat.org. Macroscopic view of primary tumor and metastasis to lungs Microscopic view lung metastasis H&E stained