The Fabp1 (fatty acid binding protein 1, liver) gene encodes the highly conserved cytosolic chaperone protein L-FABP, which is primarily expressed in the liver. L-FABP binds long-chain fatty acids as well as other hydrophobic ligands and has a role in hepatic lipid binding and metabolism.
Mice that are homozygous for the targeted mutation are viable and fertile. No gene product (mRNA or protein) is detected by RT-PCR or Western blot analysis of liver tissue.
Although hepatic sterol carrier protein-2 (SCP-2) levels are increased by 1.4 fold in homozygotes, the hepatic level of SCP-2 precursor protein, SCP-x, is reduced by 4 fold. Homozygotes display decreased fasting serum glucose levels, and reduced fatty acid binding capacity of hepatic cytosol proteins. Female homozygotes accumulate hepatic total cholesterol. Male homozygotes exhibit reduced hepatic triacylglycerol levels. Cultured primary hepatocytes from livers of homozygous animals exhibit reduced hepatic uptake and oxidation of dietary long chain fatty acids (palmitic acid). When fed a high fat diet for 12 weeks, female mutant mice gain weight more rapidly than female wildtype controls and male homozygotes. Fat tissue mass in female homozygotes is increased by 4.5 fold, and in male homozygotes by 3.4 to 3.7 fold, compared to wildtype controls. On a chow diet, homozgyotes exhibit decreased liver weight, with male homozygotes exhibiting a lowered ratio of liver weight to body weight, than wildtype controls. On a high fat diet, liver weight is further decreased in homozygotes and both male and female homozygotes exhibit lowered ratio of liver weight to body weight. Serum beta-hydroxybutyrate levels are decreased in homozygotes, indicating decreased fatty acid oxidation.
