TY - JOUR
T1 - Understanding hyperlipidemia and atherosclerosis: lessons from genetically modified apoe and ldlr mice
AU - Wouters, K.A.M.
AU - Shiri-Sverdlov, R.
AU - van Gorp, P.J.J.
AU - van Bilsen, M.
AU - Hofker, M.H.
PY - 2005/1/1
Y1 - 2005/1/1
N2 - Hyperlipidemia is the most important risk factor for atherosclerosis, which is the major cause of cardiovascular disease. The etiology of hyperlipidemia and atherosclerosis is complex and governed by multiple interacting genes. However, mutations in two genes have been shown to be directly involved, i.e., the low-density lipoprotein receptor (LDLR) and apolipoprotein E (ApoE). Genetically modified mouse models have been instrumental in elucidating the underlying molecular mechanisms in lipid metabolism. In this review, we focus on the use of two of the most widely used mouse models, ApoE- and LDLR-deficient mice. After almost a decade of applications, it is clear that each model has unique strengths and drawbacks when carrying out studies of the role of additional genes and environmental factors such as nutrition and lipid-lowering drugs. Importantly, we elaborate on mice expressing mutant forms of APOE, including the APOE3Leiden ( APOE3L ) and the APOE2 knock-in ( APOE 2k) mouse models. These models have outstanding potential, as they are highly responsive to dietary factors and pharmacological interventions.
AB - Hyperlipidemia is the most important risk factor for atherosclerosis, which is the major cause of cardiovascular disease. The etiology of hyperlipidemia and atherosclerosis is complex and governed by multiple interacting genes. However, mutations in two genes have been shown to be directly involved, i.e., the low-density lipoprotein receptor (LDLR) and apolipoprotein E (ApoE). Genetically modified mouse models have been instrumental in elucidating the underlying molecular mechanisms in lipid metabolism. In this review, we focus on the use of two of the most widely used mouse models, ApoE- and LDLR-deficient mice. After almost a decade of applications, it is clear that each model has unique strengths and drawbacks when carrying out studies of the role of additional genes and environmental factors such as nutrition and lipid-lowering drugs. Importantly, we elaborate on mice expressing mutant forms of APOE, including the APOE3Leiden ( APOE3L ) and the APOE2 knock-in ( APOE 2k) mouse models. These models have outstanding potential, as they are highly responsive to dietary factors and pharmacological interventions.
U2 - 10.1515/CCLM.2005.085
DO - 10.1515/CCLM.2005.085
M3 - Article
C2 - 15899668
SN - 1434-6621
VL - 43
SP - 470
EP - 479
JO - Clinical Chemistry and Laboratory Medicine
JF - Clinical Chemistry and Laboratory Medicine
IS - 5
ER -