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Physiogenomics of Stressors in Derived Consomic Rats Dissect multigenic common Heart, Lung, Blood, & Sleep diseases through the development of panels of.

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Presentation on theme: "Physiogenomics of Stressors in Derived Consomic Rats Dissect multigenic common Heart, Lung, Blood, & Sleep diseases through the development of panels of."— Presentation transcript:

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

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

3 PhysGen Organization

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

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

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

9 Renal Studies - Chronic Monitoring Facility with high salt stressor 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% O 2

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  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 Biochemical Studies

16 Histology Studies Characterization of the morphological responses of abdominal aorta, heart and kidney tissues to normoxia, hypoxia, high salt and L-NAME treatments Tissue slides available via order form http://pga.mcw.edu/pga-bin/order_tissue.cgi 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.


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