Model Organisms in Drug Discovery

et al., 1998; Sugiyama et al., 2001). Ten measurements of blood pressure are
made per day on each of 4 days for each animal evaluated. Results are
recorded as the pooled average of 40 measurements.
Zymosan challenge assay
Peritoneal leukocyte recruitment assays are used to identify targets that may
regulate the inflammatory component of atherosclerosis. These assays detect
abnormalities in immune cell recruitment to a site of inflammation. It has been
shown in mutant such as C-C chemokine receptor 2 (CCR2) knock-outs that a
defect in immune cell recruitment in these assays correlates well with a
significant reduction in the inflammatory component of atherosclerosis and
the subsequent plaque formation (Boring et al., 1997).
Blood lipids
High cholesterol and triglyceride levels are recognized risk factors in the
development of cardiovascular disease. Measuring blood lipids allows us to
find the biological switches that regulate blood lipid levels; inhibition of these
switches should lead to a reduction in the risk for cardiovascular disease.
Optic fundus photography and angiography
Optic fundus photography is performed on conscious animals using a Kowa
Genesis small-animal-fundus camera modified according to Hawes et al.
(1999). Intraperitoneal injection of fluorescein permits the acquisition of
direct light fundus images and fluorescent angiograms for each examination.
In addition to direct ophthalmological changes, this test can detect retinal
changes associated with systemic diseases such as diabetes and atherosclerosis.
Level 2 cardiology tests
HIGH-THROUGHPUT BIOLOGY 263
. Platelet aggregation
. Vascular injury by carotid cuff
. Chemically induced thrombosis
. Poloxamer-induced atherosclerosis
. Aortic banding
. Permanent coronary occlusion
. Crosses with apolipoprotein E, low-density lipoprotein receptor and
knock-outs