Age of onset, pattern of distribution, and histology of aneurysm development in a genetically predisposed mouse model

The blotchy mouse has an X chromosome mutation affecting crosslinking of collagen and elastin, which results in aneurysmal dilatation of the aorta. The age of onset, patterns of distribution, and histologic features of these lesions have not been characterized in detail in previous studies. Male normal and blotchy mice 1 to 8 months of age were killed and latex was injected into the left ventricles to facilitate exposure, examination, histologic sampling, and photography of the aorta. Aneurysms were not detected in any normal animals but the affected animals had a progressive increase in the incidence of aneurysms with age, reaching 100% by 6 months. Most aneurysms occurred in the ascending aorta, with some also present in the descending thoracic and abdominal segments. Some animals had multiple aneurysms. Histologically the blotchy mice aortas exhibited disrupted elastic lamellae and thickening of the interlamellar spaces. These spaces contained conspicuously pleomorphic smooth muscle cells, confirmed by electron microscopy. These changes occurred as early as 21 days, when there was no gross evidence of aneurysmal development. Aortic aneurysms develop in blotchy mice in a consistent fashion, with characteristic gross and histologic changes. These animals provide a practical model for further studies of aneurysmal disease, including possible therapeutic interventions to prevent aneurysm development.