We investigated the effects of a high-cholesterol (HC) diet administered long term (25 or 55 weeks) on metabolic disorders including hepatic damage in mice. The mice were fed the HC diet (15 % milk fat, 1·5 % cholesterol and 0·1 % cholic acid, w/w) for 25 or 55 weeks. Body and adipose tissue weights were similar to those of mice fed a control diet. Consumption of the HC diet long term resulted in hypercholesterolaemia, hepatic steatosis and gallstones. In addition, focal nodular hyperplasia (FNH) and mild fibrosis of the liver developed in all mice fed the HC diet for 55 weeks. Plasma levels of monocyte chemoattractant protein (MCP)-1 were elevated, and the level of hepatic platelet-derived growth factor (PDGF)-B protein was increased in mice fed the HC diet compared with those fed the control diet. Thus, it seems likely that the liver fibrosis and FNH caused by the long-term consumption of a HC diet may be partly due to an elevation of plasma MCP-1 and hepatic PDGF expression.

In this report, we describe the distribution of the platelet-derived growth factor receptor α (PDGFRα) by immunolocalization in the embryonic day 10.5 mouse heart and defects in heart development associated with the absence of this receptor in the Patch mouse. The Patch mouse is a naturally occurring mutant that has been accepted as a model for determining the role of the PDGFRα in early cardiac development. Even though other genetic defects exist in this naturally occurring mutant, most defects associated with cardiac development are believed to be a result of the absence of this receptor. Gross morphological defects including improper septation of the outflow tract, dysmorphic shape of the heart, and lack of trabecular development are similar to those that have been previously described. Many of these defects have been attributed to the failure of a subset of non-neuronal neural crest cells to properly migrate into the region of the developing outflow tract. In these studies, we have also used confocal scanning laser and transmission electron microscopy to describe and compare the organization and differentiation of the cytoskeletal proteins actin and myosin in littermate control and Patch mouse hearts. Cytoskeletal organization of the cardiac myocytes in Patch mouse hearts has not previously been described. In most cardiac myocytes of Patch mice, actin was found only on the periphery of the cells, and the organization of actin, myosin, and precursor Z-band material into distinct myofibrils was greatly reduced.