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Cardiovascular Trait (CVT) Consortium Patricia Munroe. Primary traits of interest. Hypertension. Cardiac arrhythmias (ECG). Heart Failure. Aims of the CVT consortium. - PowerPoint PPT Presentation
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Aims of the CVT consortiumTo characterise a series of KO mouse models
derived from genes selected from human GWAS studies and functional experimentation.
Specific objectives: To establish whether the KO mouse has the CV phenotype
we predicted based on gene selection. To establish additional phenotypic deviations from normal,
including target-organ damage to heart, brain and kidney. To characterise the functional consequences and
pathways affected by absence of the KO gene.
Consortium phenotype expertise and interests
BP/hypertension/CADBP/hypertension/CAD ECG measures/arrhythmiasECG measures/arrhythmias
LVD, LVH and Heart FailureLVD, LVH and Heart Failure
New membersAlistair Poole (UK)Tim Warner (UK)
Cristiana Ruhrberg (UK)Ines Pineda-Torra (UK)Ross Breckenridge (UK)
CVT consortium members are from UK, NL, FR and USA
CV screening by IMPCCV screening
Standard screensHeart weight, electrolytes, cardiac histopathology, eye fundus (retinal vessels)
Additional screens requested (under consideration)Blood pressure (e.g., tail cuff)ECG (ECGenie)ECHO/US? Additional blood clinical chemistry - serum creatinine and natriuretic peptides (BNP and/or ANP- when test validated , NT-proBNP)
Additional urine collection and chemistry (preferably 24hours at metabolic cage, alternatively urine collection during anesthesia/sacrifice) - urinary creatinine and urinary albumin (and/or total protein)Additional organ collection at necropsy - Heart (dissection into atria and ventricles, and left verses right heart weight), kidney, brain, aorta, liver
Kidney and lung weight/body weight or tibia length ratio
Kidney histopathology
Challenges / Niche screens - High saline water or high-salt diet (if indicated by trait)
Current activities• Developing packages of work for year 1
– How best to distribute CV phenotyping between centres?– Creation of working groups per gene of interest– Obtaining additional functional data on genes of interest
for inclusion in grants– Funding options for technical staff and CV phenotyping
• New member interests– Development of HT platelet phenotyping protocol (A.
Poole), and a platelet aggregation assay (T. Warner)– Inclusion of CAD genes from GWAS (N. Samani)– Lipids and metabolomics (M. Ala-Korpela)