Genomics Component


Director: Howard J. Jacob, Ph.D.
Co-Investigators: Allen W. Cowley, Jr., Ph.D., Andrew S. Greene, Ph.D., Anne E. Kwitek, Ph.D.
Component Contact person: Melinda Dwinell, Ph.D.

Description

The Genomics Component is both a service component and a primary data-generating component of this PGA. It is charged with generating the ENU mutant strains in the same three inbred strains used to generate the consomic rat strains. ENU mutant rats are being generated using ENU mutagenesis and screening 100 genes involved in NHLBI disorders, using the TILLING method to identify offspring with the mutated gene of interest. The functionality of these genes is being tested in the Phenotyping Component by using a broad phenotypic screen of the cardiovascular and pulmonary systems. The genes selected for mutation screening have been derived from those that have been linked to heart, lung and blood disorders using molecular genetic, genomic and expression technologies during the first four years of all PGA programs. As genomic background is shown to play a major role in the expression of phenotypes in KO mice, this PGA are attempting to make the KOs in 3 genetic backgrounds in the rat, the SS, BN, and FHH strains. The selection of these 3 strains will also enable PhysGen to leverage the enormous amount of phenotypic data generated on these strains during the first four years, notably 8,610 physiological data points per strain, including baseline and stressors, providing an unprecedented level of baseline data for a mutagenesis screen

Strains

  • PARENTALS
    SS (Dahl Salt-Sensitive; SS/JrHsd/Mcwi)
    BN (Brown Norway; BN/ SsNHsd/Mcwi)
    FHH (Fawn-Hooded Hypertensive; FHH/EurMcwi)

    These 3 strains were selected for the development of the consomic panels because of the abundance of traits unique between these strains that bear close resemblance to human disease traits of great interest to the NHLBI. These 3 strains are also being used for the generation of the ENU mutant strains.

  • ENU MUTANT STRAINS

    For current list of ENU mutant strains, please click here

  • CONSOMICS
    SS-1BN/Mcwi (SS.BN-1) to SS-20BN/Mcwi (SS.BN-20), X, Y
    FHH-1BN/Mcwi (FHH.BN-1) to FHH-20BN/Mcwi (FHH.BN-20), X, Y

    The nomenclature is as follows, SS-1BN/Mcwi (SS.BN-1) is a SS genomic background with a BN chromosome introgressed, a number signifies the autosome introgressed, in this case chromosome 1; the sex chromosomes are designated by an X or Y; a complete consomic line would be SS-1BN/Mcwi (SS.BN-1) to SS-20BN/Mcwi (SS.BN-20), X, Y.

  • CONGENICS
    SS.BN-(D12arb13-D12 rat 79)/Mcwi
    Others as time permits.

  • Other Strains
    SD (Hsd:Sprague Dawley)
    GH (Genetically Hypertensive)
    SHR (SHR/NCrlBR; Spontaneously Hypertensive Rat)
    Others as time permits.

    For more information regarding animal strains please see the Rat Genome Database at http://rgd.mcw.edu/.

Breeding Scheme

Click for details.

Components
Genomics
Phenotyping
Research Services
Bioinformatics
Education
Administration