Description:
Market: The American Heart
Association reports that Coronary heart disease, caused by atherosclerosis, or
the narrowing of the coronary arteries due to fatty build ups of plaque, caused
452,300 deaths in the U.S. in 2004. Coronary Heart Disease
was the cause of 1 out of every 5 deaths in America in 2004, with direct and indirect costs
in the U.S. totaling near $151.6
billion.
Current Problems: It is well
recognized that plasma apolipoprotein B (apoB) levels are a strong predictor of
atherosclerosis. Therefore,
extensive clinical and molecular investigations have been carried out to
understand the association of apoB with heart disease. The most common cause of increased
plasma apoB is over-secretion of apoB-containing low density lipoprotein
particles (LDL) by the liver.
Humans express apoB mRNA editing enzyme (Apobec1) only in the gut, while
mice produce this enzyme in both the liver and small intestine. Apobec1 activity results in a smaller
apoB (apoB48), and apoB48-containing lipoproteins catabolize efficiently by a
different receptor. Hence, mice
have minute amount of LDL. This
difference is recognized as one of the main reasons that wild-type mice are
resistant to atherosclerosis.
Wild-type mice have high density lipoprotein (HDL) as the major
lipoprotein, not LDL, and therefore do not mimic the human condition as closely
as an animal model could.
The Technology: Researchers at the
University of Texas Health Science Center at Houston (UTHealth) have developed two mouse
models to study the pathenogenesis of atherosclerosis. Both mouse lines lack the LDL receptor
and the ability to edit apoB mRNA (designated LDb:
LDLR-/-Apobec1-/-). One mouse line additionally
over-expresses human apoB100 gene (designated LTp:
LDLR-/-Apobec1-/-ERhB+/+). Both mouse lines have elevated LDL
levels with decreased HDL cholesterol, with a lipoprotein distribution profile
similar to that seen in human patients with hyperlipidemia. The mice readily develop
diet-independent atherosclerosis as early as 3 months, with diet-dependent
acceleration possible. The phenotypes developed are similar to that of human
atherosclerosis, making them an ideal model for atherosclerosis in humans. For
more information about the mouse lines as well as availability and Materials
Transfer License Agreement terms, please contact the Office of Technology
Management at UTHealth.
UTHealth Ref.
No.: 2006-0021