Cardiovascular Trait (CVT) Consortium

Patricia Munroe

Primary traits of interest

Hypertension Heart Failure Cardiac arrhythmias (ECG)

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)

Flow chart of the experiments

Consortium secondary screens

Consortium secondary screens

Models and challenges

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)

Additional slides

A. Hobbs,A. Ahluwalia,T. Johnson,M. Caulfield,

X. Jeunemaitre,H. Buikema,H. van Goor,

S. Ye

A. Tinker,Y. Jamshidi ,

F. Conti,A. Maass

P. Munroe, C.Newton-Cheh,A. Hingorani

E. Cartwright,L. Neyses,P. vd Meer

K. Suzuki R. d Boer

P. vd Harst