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Physiogenomics of Stressors in Derived Consomic Rats

Physiogenomics of Stressors in Derived Consomic Rats. Focus: Rat Models of HLBS Disorders. Dissect multigenic common Heart, Lung, Blood, & Sleep diseases through the development of panels of chromosomal substitution strains of rats (consomic rat panels). SS.BN16. SS.BN20.

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Physiogenomics of Stressors in Derived Consomic Rats

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  1. Physiogenomics of Stressors in Derived Consomic Rats Focus: Rat Models of HLBS Disorders Dissect multigenic common Heart, Lung, Blood, & Sleep diseases through the development of panels of chromosomal substitution strains of rats (consomic rat panels).

  2. SS.BN16 SS.BN20 Consomic panels from SS.BN1 to SS.BN 21 SS.BN1 SSBN4 SS.BN4 SS.BN8 SS.BN12 SSBN12 SSBN12 SS SS BN BN

  3. PhysGen Organization Genomics Component Genotyping & Animal Production (Transponders and transfer) 3735 15 strains/yr Phenotyping Component Conditioning Protocols 330 330 255 420 330 330 330 330 420 330 330 High salt, hypoxia & normoxia Histology Studies Hypoxia, normoxia Microarray Studies low salt high salt Isolated Vessel Hypoxia, normoxia Hypoxia, normoxia high salt & salt depletion Respiratory Studies Genomics Component Cardiac Studies Lung Studies Renal Studies Expression Profiling Blood Studies Research Services Component TIGR Consomic Bioinformatics Component Expression Data Consomic Rat DNA & Genotyping Functional Strains Baseline & Stressed Baseline & Stressed Data Mapping Expression Data Physiological Data Rat distribution * Numbers indicate animals studied per year

  4. Genomics Component – Animal Breeding Up to 6000 genotypes per week are performed (3500 on average) and utilized to speed the development of the consomic strains

  5. Genomics Component - Genotyping PCR-based testing with selected genetic fluorescent markers Consomic progenitors have a QC total genome scan with 95 markers

  6. Consomic Rat Distribution in collaboration with Charles River Laboratories Once strains are developed they are transferred to Charles River Laboratories to distribute animals to the public http://www.criver.com/products/consomic/index.html

  7. Microarray Expression Studies in collaboration with The Institute for Genomic Research PGA http://pga.tigr.org/RatText.shtml#Overview

  8. Phenotyping Component Studies • Renal • Respiratory • Vascular • Lung • Cardiac • Biochemical • Histology http://pga.mcw.edu/pga-bin/data_status.cgi

  9. Renal Studies - Chronic Monitoring Facility with high salt stressor 32 channels/unit x 10 recording units ( 300 cages: metabolic and non-metabolic)

  10. Respiratory Studies - Plethysmograph boxes for acute hypoxia and hypercapnia stressors

  11. Vascular Studies - Aortic Ring Preparation 16 bath set-up for simultaneous study of 8 rats/day; with high salt stressor

  12. Hypoxic conditioning for Lung and Cardiac Phenotyping Studies Simultaneous conditioning of 108 animals at 12% O2

  13. Lung Studies Characterization of pulmonary vascular resistance and airway responsiveness to cholinergic challenge in 5 rats per day

  14. Cardiac Function Studies - 6 perfused hearts in parallel

  15. Biochemical Studies • Small Animal Profile (ANP-1) • Glucose, AST, ALT, Alkaline Phosphatase, Total Bilirubin, Total Cholesterol, Total Protein, Albumin, Urea Nitrogen, Creatinine, Phosphorus, Calcium, Sodium, Potassium, Chloride, Bicarbonate, Anion Gap • Complete Blood Count With Differential (CBC) • RBC, Hemoglobin, Hematocrit, MCV, MCH, MCHC, RDW, Platelet, WBC and Differential

  16. Histology Studies Characterization of the morphological responses of abdominal aorta, heart and kidney tissues to normoxia, hypoxia, high salt and L-NAME treatments Effects of High Salt on Kidneys from FHH and SS Strains • The FHH kidney (left) shows only mild pathological changes. • The SS kidney (right) shows widespread tubular protein casts (red) and fibrosis (blue) in the vasa recta. Trichrome Stain. Tissue slides available via order form http://pga.mcw.edu/pga-bin/order_tissue.cgi

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