We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
High-Throughput Production and Phenotyping of Rat Knockout Models for Hypertension.
- Authors
Moreno, Carol; Dwinell, Melinda R.; Majewski, Rebecca R.; Kwitek, Anne E.; Jessner, Martin J.; Feroah, Thorn R.; Forster, Hubert V.; Mattson, David L.; Lombard, Julian H.; Macquestion, Gregory D.; Roman, Richard J.; Greene, Andrew S.; Cowley, Allen W.; Jacob, Howard J.
- Abstract
The inability to generate knock-out (KO) rats has been a major limitation for studying gene function in rats. PhysGen-MCWuses a strategy that combines ENU mutagenesis to induce spermatic gene mutations, with TILLING, a high-throughput assay which identifies mutations between wild-type and mutated alleles to confirm and identify KO rats. The goal is to identify the induced point mutations in 112 selected genes in three different rat strains Dahl Salt-Sensitive, Brown Norway, and Fawn-Hooded Hypertensive rat with the broad goal of developing 99 total strains of KO rats (33 genes on 3 different genome backgrounds), which are then characterized physiologically for of cardiovascular, pulmonary and behavioral traits. We have currently developed 26 gene-mutation strains, of which six are KO for different genes. Males are injected with a variable dose of ENU and then bred to wild-type females to produce the KO rats, which is then brought to homozygosis. An ultrasound protocol assesses cardiac function by echocardiography in basal and stressed (dobutamine administration) conditions. Vascular function is studied in aortic rings with responsiveness to vasoconstrictors and vasodilators. Plasma levels 29 hormones, electrolytes and blood indicators are also measured. Blood pressure is determined and kidney function is assessed by protein excretion. KO rats availability and data is posted in the PGA web site periodically (pga.mcw.edu).
- Subjects
HYPERTENSION; PHENOTYPES; GENETIC regulation; MUTAGENESIS; ECHOCARDIOGRAPHY; BLOOD pressure; LABORATORY rats
- Publication
FASEB Journal, 2007, Vol 21, Issue 6, pA1236
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fasebj.21.6.a1236