The human apoE7 and apoE4 transgenic mice models

Area of Science:

• Molecular genetics
• Neuroscience
• Metabolic disorders

Background:

• Human apolipoprotein E (apoE) plays a crucial role in lipid metabolism.
• Mutations in apoE are associated with various diseases, including Alzheimer's disease and cardiovascular conditions.
• Understanding the specific impact of apoE isoforms, such as apoE4 and apoE7, is essential for elucidating disease mechanisms.

Purpose of the Study:

• To investigate the in vivo molecular genetic phenomena and pathological effects of human mutant apoE4 and apoE7.
• To establish and characterize transgenic mouse models expressing human apoE4 and apoE7.
• To analyze the impact of these mutations on lipid metabolism, cognitive function, and lifespan.

Main Methods:

• Generation of transgenic mice via microinjection of human apoE4 and apoE7 genes.
• Confirmation of transgene integration and expression using Southern blot, Northern blot, and ELISA.
• Assessment of serum lipid levels and lipid metabolism regulation.
• Evaluation of learning and memory through behavioral tests.
• Monitoring of lifespan in transgenic lines.

Main Results:

• Stable transmission of transgenes and associated phenotypes in established transgenic lines.
• Transgenic mice exhibited hyperlipidemia, characterized by elevated serum lipid levels.
• Significant degeneration in learning and memory capabilities was observed in behavior tests.
• Two transgenic lines displayed a shortened lifespan.
• While high-fat diets increased serum lipids in both normal and transgenic mice, distinct regulatory mechanisms were identified.

Conclusions:

• Human apoE4 and apoE7 mutations lead to hyperlipidemia, cognitive deficits, and reduced lifespan in mice.
• The pathogenesis of lipid metabolism disorders caused by apoE mutants is consistent regardless of their location (N-terminal or C-terminal).
• These transgenic models provide valuable tools for studying apoE-related disorders and developing therapeutic strategies.