Transgenic mice expressing human apoB100 and apoB48

Area of Science:

• Biochemistry
• Genetics
• Cardiovascular Research

Background:

• Apolipoprotein B (apoB) is a key component of low-density lipoprotein (LDL).
• Understanding apoB's role in lipoprotein metabolism and atherosclerosis is crucial for cardiovascular health.
• Existing animal models may not fully recapitulate human apoB-related lipoprotein profiles.

Purpose of the Study:

• To develop transgenic mice expressing functional human apolipoprotein B.
• To characterize the lipoprotein profiles in these novel transgenic mice.
• To establish a valuable animal model for studying human lipoprotein disorders and atherosclerosis.

Main Methods:

• Microinjection of fertilized mouse oocytes with an 80 kb genomic DNA fragment containing the entire human APOB gene.
• Generation and breeding of transgenic mice.
• Quantification of human apoB100 plasma concentrations.
• Analysis of lipoprotein distribution, particularly LDL cholesterol levels.

Main Results:

• Successful generation of transgenic mice expressing human apoB.
• Achieved high plasma concentrations of human apoB100, comparable to normolipidemic humans.
• Demonstrated that human apoB100 predominantly resides in the LDL fraction.
• Observed substantially increased levels of LDL cholesterol in these mice.

Conclusions:

• Human apoB-transgenic mice effectively model human lipoprotein metabolism.
• These mice provide a platform for investigating the role of LDL in the development of atherosclerosis.
• The model is suitable for preclinical studies related to dyslipidemia and cardiovascular disease.