Experimental cerebral aneurysms in the female heterozygous Blotchy mouse.

The Blotchy mouse is characterized by an X-linked inherited disorder of connective tissue synthesis. The susceptibility to aneurysm formation in the cerebral arteries of the circle of Willis was compared in female heterozygous 'Blotchy' and control mice subjected to unilateral carotid artery ligation either alone or associated with hypertension. Cerebral aneurysms developed only in hypertensive Blotchy mice (6/31 vs. 0/30 in hypertensive controls). Aneurysms of the aorta and its major branches occurred in normotensive mice only in the Blotchy group in which hypertension increased the incidence of mesenteric and coeliac aneurysms. A light microscopic study of interruptions of the internal elastic lamina (IIEL) showed that they developed in arteries of both Blotchy and control mice but to a greater extent in the Blotchy group where hypertension further increased their incidence. The IIEL incidence in the aortic arch varied in parallel to the occurrence of aneurysms in all the different arterial sites. Thus, in an apparently normally viable animal, the presence of a mutated gene which indirectly leads to defective elastin and collagen fibre synthesis, favours the formation of both peripheral and cerebral aneurysms. However, the development of cerebral aneurysms requires the addition of an increase in haemodynamic stress.