Figure 6. Model to account for the cardiovascular and liver phenotypes in BALB/cJ and BALB/c mice on a high fat diet.

The Zhx2 gene contains a hypomorphic mutation in BALB/cJ mice (Zhx2^Afr1) but not in the highly related BALB/c substrain (Zhx2⁺). When placed on a high fat chow in the presence of the wild-type Zhx2 allele (BALB/c), hepatic lipid levels remain relatively low but serum lipid levels are elevated, contributing to the increased atherosclerosis. When BALB/cJ mice are maintained on a high fat chow, lipids are redistributed so that hepatic lipid levels are increased and serum lipid levels are lower. This increase in hepatic lipids may be due, in part, to elevated Lpl levels. Higher hepatic lipid levels enhance liver damage as determine by increased hepatocyte ballooning, neutrophil infiltration and serum ALT levels, whereas reduced serum lipid levels reduce atherosclerosis.