Frimorfo of Fribourg, Switzerland performed a phenotypic analysis on Taconic B6.129P2-Apoe^tm1Unc N11 (Apoe Knockout Mice) using the Morphome Discovery Program. Three approximately 10 week old Apoe Knockout Mice (2 females and 1 male) and 3 age matched control C57BL/6NTac Mice (2 females and 1 male) were analyzed.

Two Apoe Knockout Mice (ID F018-01 and F019-01) had mild to moderate atherosclerotic lesions in various body regions. The locations and stage of the lesions were consistent with previous reports in the published literature. (Reddick RL, Zhang SH, Maeda N. (1994) Atherosclerosis in mice lacking apoE. Evaluation of lesional development and progression. Arterioscler Thromb., 1994 Jan;14(1):141-7) Only major arteries were evaluated and characteristic lesions were noted in the two females, but not the male animal. All lesions were mild to moderate in severity and consisted of intimal plaques, adventitial fibrosis, and occasional inflammatory foci of the vascular wall. Severe lesions with vascular occlusion or aneurysm formation were not seen in this age group. No additional model-specific histological lesions were observed.

AORTA–a: Stain: Elastic Fiber. F19-01

Early Atherosclerotic plaque formation, tunica intima, thoracic aorta.

Representation of an accumulation of lipoid filled or foam cells of the xanthomatous type occupying and expanding the subendothelial space, effectively separating the endothelial cell layer from the internal elastic membrane of the tunica intima. The wall of the aorta is mildly thickened by this accumulation of material and the internal elastic membrane appears to be intact within this segment.

This response represents early atherosclerotic plaque formation localized within the tunica intima. The rest of the artery appears to be within normal limits.

AORTA–b: F19-01

Atherosclerotic plaque, tunica intima/media, thoracic aorta.

Presented with a segment of arterial wall that exhibits a mild, focally-extensive compression of the tunica media by opposing accumulations of eosinophilic, foamy, or lipid appearing material situated within the subendothelial space of the tunica intima and the tunica adventitia. An early, minimal to mild fibroplasia is evident in these areas within both the tunica intima and tunica adventitia. The endothelium is elevated by this material occupying the subendothelial space.

SMALL ARTERY: F18-01

Atherosclerotic plaque, tunica intima/media, thoracic aorta.

A focally-extensive area of the tunica media is moderately to markedly compressed by an accumulation of eosinophilic, lipoid, or fatty material within both the tunica intima and tunica adventitia.

The tunica adventitia also contains a focal, nodular, well-demarcated area of infiltrating cells characterized by mild numbers of macrophages, occasional lymphocytes, and increased collagen fibers.

The rest of the artery appears to be within normal limits. This area of constriction and corresponding proliferation may represent an area of early plaque formation.

THORACIC AORTA: F18-01

Atherosclerotic plaque, tunica intima/media, thoracic aorta.

A focally-extensive area of the endothelium appears to be elevated off the tunica media by an accumulation of eosinophilic, lipoid, or foamy appearing material which occupies the subendothelial space between the tunica intima and the tunica media. There appears to be a focally-extensive disruption of the internal elastic membrane by the accumulation of eosinophilic, lipoid or foamy appearing material within the subendothelial space between the tunica intima and the tunica media.

An area of similar material accumulation also appears present opposite the sub-endothelial proliferation. The clear, vesicular spaces within the sub-endothelial material layer were considered representative of multiple, variably-sized cholesterol clefts. Also present within the area of foam cell accumulation was a mild infiltration of collagen and fibroblasts, representing early fibroplasia.

None of the arteries contain indications of either calcification or cellular necrosis, which is usually associated with atherosclerotic change in vessels. This absence may be representative of either a lack of lesion chronicity, or depicts how the lesion is presented in this animal model.