Genetically modified mice for the study of apolipoprotein B

Abstract

Over the past five years, several laboratories have used a variety of transgenic and gene-targeted mice to study apoB. These studies have helped in 1 ) generating new mouse models suitable for investigating the genetic and environmental factors affecting atherogenesis; 2 ) providing systems for investigating apoB structure/function relationships; 3 ) understanding the regulation of apoB gene expression in the intestine; 4 ) delineating a critical role for apoB expression in mouse embryonic development; 5 ) yielding insights into the "physiologic rationale" for the existence of the two different forms of apoB, apoB-48 and apoB-100, in mammalian metabolism; and 6 ) providing basic insights into mechanisms involved in the human apoB deficiency syndrome, familial hypobetalipoproteinemia. -Kim, E., and S. G. Young. Genetically modified mice for the study of apolipoprotein B.

Mouse models of hyperlipidemia and atherosclerosis

“…al., using a P1 bacteriophage vector containing an 80 kB insert spanning the entire human apoB gene (42,43). Interestingly, these transgenic mice express human apoB only from the liver, as the intestinal enhancer is not present in the transgenic construct (45). The apoB transgenic mice have a plasma lipoprotein profile which more closely parallels that of humans, including a distinct LDL cholesterol peak.…”

Transmembrane protein 135 regulates lipid homeostasis through its role in peroxisomal DHA metabolism

“…7h ) were observed between these male genotypes. APOB100 is a marker for very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL), both of which are major carriers of cholesterol from the liver to peripheral tissues 42 . Thus, the decreased plasma cholesterol in Tmem135 FUN025/FUN025 / Lep ob/ob mice can be explained by their decreased plasma APOB100-containing lipoproteins.…”

Zebrafish mutants provide insights into Apolipoprotein B functions during embryonic development and pathological conditions

“…ApoB plays in various pathological conditions has prompted the generation of several genetically modified mouse models (11,12). However, because APOB is expressed in the yolk sac during early embryonic development, where it facilitates the supply of nutrients to the developing embryo, ApoB-knockout mice die at gestational stage 9.5 to 10.5, thereby precluding the study of the roles of this protein during embryogenesis.…”

“…In particular, the impaired synthesis of VLDL observed in patients with FHBL, which results in triglyceride accumulation in the liver, represents one among many causes of NAFLD in humans ( 10 ). The crucial role ApoB plays in various pathological conditions has prompted the generation of several genetically modified mouse models ( 11 , 12 ). However, because APOB is expressed in the yolk sac during early embryonic development, where it facilitates the supply of nutrients to the developing embryo, ApoB-knockout mice die at gestational stage 9.5 to 10.5, thereby precluding the study of the roles of this protein during embryogenesis.…”