Using genetically engineered mice to understand apolipoprotein-B deficiency syndromes in humans.
Several human diseases are characterized by defects in the synthesis and secretion of the apolipoprotein (apo) B-containing lipoproteins. Familial hypobetalipoproteinemia is caused by mutations in the apo-B gene and is characterized by abnormally low plasma concentrations of apo-B and low-density lipoprotein (LDL) cholesterol. Another apo-B deficiency syndrome, abetalipoproteinemia, is caused by mutations in the gene for microsomal triglyceride transfer protein (MTP). MTP is a microsomal protein that is thought to transfer lipids to the apo-B protein as it is translated, allowing it to attain the proper conformation for lipoprotein assembly. A third apo-B deficiency syndrome, Anderson's disease (or chylomicron retention disease), is characterized by the inability to secrete apo-B-containing chylomicrons from the intestine but an apparently normal capacity to secrete lipoproteins from the liver. To more fully understand these human apo-B deficiency syndromes, our laboratory has generated and characterized gene-targeted mouse models. This review summarizes what has been learned from these animal models.
Raabe
M
M
Gladstone Institute of Cardiovascular Disease, University of California, San Francisco 94141-9100, USA.
Kim
E
E
Véniant
M
M
Nielsen
L B
LB
Young
S G
SG
D000012:Abetalipoproteinemia / Q000235:genetics; D000818:Animals; D001055:Apolipoproteins B / Q000172:deficiency* / Q000235:genetics*; D004195:Disease Models, Animal; D030342:Genetic Diseases, Inborn / Q000235:genetics; D005818:Genetic Engineering; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000235:genetics; D051379:Mice; D013577:Syndrome
D001055:Apolipoproteins B