Effect of enriched housing on fibulin‐4 knockout mice

Abstract

Fibulin-4 is one of a family of newly recognized extracellular matrix proteins that are expressed by smooth muscle cells and are found in large and small blood vessels. Experiments were performed to test the following hypothesis: arterial pathologies in fibulin-4 knock-out mice are altered by housing conditions. Knock-out mice and wild-type mice were housed four per cage in standard cages, as is the usual practice. After 3 weeks the mice were sacrificed, and the aortas perfusion-fixed and excised for light and electron microscopy. Localized regions of disorganized extracellular matrix and collagen fibers consistently appeared between some of the medial smooth muscle cells in the knockout mice. In the wild-type mice the smooth muscle cells were closely connected to each other and the media was inherently more compact. The number of disorganized regions per 1,000 square microns was significantly greater for knock-out mice (0.172 ± 0.043 (SEM)) than for wild-type mice (0.015 ± 0.008) (p<0.05, n = 8). This study was repeated with the mice housed two per cage in larger cages, each cage containing a tunnel and a wheel. In this case the knock-out mice showed significantly fewer disorganized regions than those in standard cages (0.035 ± 0.012) (p<0.01, n = 8). The wild type mice also showed fewer disorganized regions (0.003 ± 0.002) but this difference was not significant. These results indicate that arterial pathologies manifested in fibulin-4 knock-out mice can be reduced by improving housing conditions, and imply that appropriate environments can counteract the effects of some genetic deficiencies. Supported by NCCAM P20AT00774