PhysGen News

 PhysGen Announces the Availability of Mutant Rats

PhysGen, one of five Programs for Genomic Applications (PGA) funded by the National Heart, Lung and Blood Institute is currently generating knockout rats using an ENU (N-ethyl-N-nitrosourea) mutagenesis strategy. Male rats were subjected to ENU and bred to healthy female rats to generate F1 heterozygous offspring. Prior to phenotypic screening, the offspring are screened by TILLING, a high-throughput method which identifies mutations by enzyme cleavage of heteroduplex PCR product formation between wild-type and mutated alleles. During the screening process, several amino acid changes were identified in targeted genes. Confirmed gene knockouts will be phenotypically characterized and data will be released on the PhysGen website. We are pleased to make the rats with amino acid changes available to interested investigators (click here for details). Heterozygous mutant rats (5M/5F) will be available on a first come-first serve basis for 75 days after posting on PhysGen's website (http://pga.mcw.edu). For additional information on how to obtain these rats, please contact Melinda Dwinell at (414) 456-4498 (mrdwinel@mcw.edu).

 Completion of consomic development and characterization

PhysGen has completed the development and physiological characterization of two panels of consomic rat strains (SSxBN, FHHxBN). High-throughput phenotypic screens of cardiovascular, pulmonary, renal, vascular and blood systems have been completed for all 44 consomic rat strains as well as 11 commonly used rat strains. Physiological data can be viewed by clicking here

 Upcoming Events

Rat Genomics and Models
Date: Dec. 6-9, 2007
Location: Cold Spring Harbor Laboratory
Additional Information: here

 Archived News and Events

• RAT GENOMICS & MODELS, December 8-11, 2005, Cold Spring Harbor Laboratory      Organizers:
       Timothy Aitman, Imperial College, London, UK
       Howard Jacob, Medical College of Wisconsin
       James Shull, University of Nebraska Medical Center
  
• EXPERIMENTAL BIOLOGY 2006 , April 1-5, 2006, San Francisco, CA
       PhysGen & Rat Genome Database will host a booth (#1317), "Rat Physiological Genomic Tools"
  

Nov 3, 2004: The Programs for Genomic Applications (PGA) grant renewal was awarded to the Medical College of Wisconsin, Howard Jacob Ph.D., Principal Investigator, on July 29, 2004. The grant renewal, Knock-Out Rats for Physiological Genomics, will extend from 08/01/2004 to 07/31/2008.

• On September 30, 2000, the National Heart, Lung, and Blood Institute (NHLBI) launched the Programs for Genomic Applications (PGAs) http://www.nhlbi.nih.gov/resources/pga/. This program is a major initiative to advance functional genomic research related to heart, lung, blood, and sleep health and disorders. The MCW program, termed PhysGen, has been focused on understanding the genetic basis of fundamental mechanistic pathways of the heart, lung, kidney, blood and vasculature through development of consomic rat panels and physiological genomics, using environmental stressors.
• The PhysGen renewal will continue the success of the program by capitalizing on a variety of technological advances, extending the data by manipulating specific genes and assessing the results physiologically in three different genetic backgrounds. The "functionality" of relevant genes will be tested by generating knockouts (KO) in rats, using a novel strategy with ENU mutagenesis. (Large-Scale Discovery of Induced Point Mutations With High-Throughput TILLING. Genome Res., Mar 2003; 13: 524 - 530; Production of knockout rats using ENU mutagenesis and a yeast-based screening assay. Yunhong Zan, Jill D Haag, Kai-Shun Chen, Laurie A Shepel, Don Wigington, Yu-Rong Wang, Rong Hu, Christine C Lopez-Guajardo, Heidi L Brose, Katherine I Porter, Rachel A Leonard, Andrew A Hitt, Stacy L Schommer, Anu F Elegbede & Michael N Gould. Nature Biotechnology 21, pp 645 - 651, 2003).
• The genes selected for KO (Click here to see gene list) 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 will attempt 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.
• If you would like to comment on the list, or suggest additional genes for consideration please contact Julie Messinger at (414) 456-4531 or jmessing@mcw.edu

June 16, 2004: Parental, consomic and congenic strain profiles are now available. The strain profile includes general information for each rat strain, as well as summaries and statistical analysis of significant phenotypes. Click here for details. Stay tuned for more.

March 31, 2004 - An international research team, supported by the National Institutes of Health (NIH), announced it has completed a high-quality, draft sequence of the genome of the Brown Norway rat http://www.nhgri.nih.gov/11511308. The strain is the BN/NHsdMcwi, which has been extensively characterized by PhysGen. Click here to select and review phenotype, genotype, microarray or strain profile data on the PhysGen website.

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Related News

Rat genome sequence: BN/NHsd/Mcwi draft sequence is available on UCSC genome browser