Generation of general and tissue-specific gene knockout mouse models

Area of Science:

• Genetics and Molecular Biology
• Cardiovascular Research
• Metabolic Disease Research

Background:

• Gene knockout technology is vital for studying genes influencing plasma lipids, lipoproteins, and atherosclerosis.
• While whole-body knockouts are established, tissue-specific knockouts are underutilized but critical for understanding lipoprotein metabolism.
• Major tissues involved in lipoprotein metabolism include the liver, intestine, and macrophages.

Purpose of the Study:

• To describe general procedures for generating whole-body gene knockout mice.
• To present approaches for creating tissue-specific knockout mice (liver, intestine, myeloid cells).
• To provide a framework applicable to establishing various gene knockout mouse models.

Main Methods:

• Generation of whole-body phospholipid transfer protein (PLTP) gene knockout mice.
• Development of tissue-specific knockout mice for serine palmitoyltransferase (SPT) subunit 2.
• Utilizing bone marrow transplantation for myeloid cell-specific knockout models.

Main Results:

• Established a general procedure for whole-body knockout mouse generation.
• Demonstrated methods for creating tissue-specific knockout mice in liver, intestine, and myeloid cells.
• Provided a versatile methodology applicable to diverse gene knockout mouse models.

Conclusions:

• Feasible approaches for generating both general and tissue-specific gene knockout mouse models are presented.
• These mouse models are essential for advancing the understanding of lipid metabolism and atherosclerosis.
• The described techniques will facilitate novel insights into gene function in relevant tissues.