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High-Throughput Production and Phenotyping of Rat Knockout Models for Hypertension.

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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.
Source: FASEB Journal; Apr2007, Vol. 21 Issue 6, pA1236-A1236, 1/5p
Subject Terms: HYPERTENSION, PHENOTYPES, GENETIC regulation, MUTAGENESIS, ECHOCARDIOGRAPHY, BLOOD pressure, LABORATORY rats
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). [ABSTRACT FROM AUTHOR]
Copyright of FASEB Journal is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: High-Throughput Production and Phenotyping of Rat Knockout Models for Hypertension.
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  Data: FASEB Journal; Apr2007, Vol. 21 Issue 6, pA1236-A1236, 1/5p
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  Data: <searchLink fieldCode="DE" term="%22HYPERTENSION%22">HYPERTENSION</searchLink><br /><searchLink fieldCode="DE" term="%22PHENOTYPES%22">PHENOTYPES</searchLink><br /><searchLink fieldCode="DE" term="%22GENETIC+regulation%22">GENETIC regulation</searchLink><br /><searchLink fieldCode="DE" term="%22MUTAGENESIS%22">MUTAGENESIS</searchLink><br /><searchLink fieldCode="DE" term="%22ECHOCARDIOGRAPHY%22">ECHOCARDIOGRAPHY</searchLink><br /><searchLink fieldCode="DE" term="%22BLOOD+pressure%22">BLOOD pressure</searchLink><br /><searchLink fieldCode="DE" term="%22LABORATORY+rats%22">LABORATORY rats</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: 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). [ABSTRACT FROM AUTHOR]
– Name: Abstract
  Label:
  Group: Ab
  Data: <i>Copyright of FASEB Journal is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1096/fasebj.21.6.a1236
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      – Code: eng
        Text: English
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        StartPage: A1236
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      – SubjectFull: HYPERTENSION
        Type: general
      – SubjectFull: PHENOTYPES
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      – SubjectFull: GENETIC regulation
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      – SubjectFull: MUTAGENESIS
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      – SubjectFull: ECHOCARDIOGRAPHY
        Type: general
      – SubjectFull: BLOOD pressure
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      – SubjectFull: LABORATORY rats
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              Text: Apr2007
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