We have completed two consomic panels (44 strains), whereby a BN chromosome was systematically introgressed onto the background of either the SS or FHH rat strains (URL). To complement these resources and data, we are generating ENU-induced mutant strains in the same three parental 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. We will test the functionality of these genes 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. Click here for details.