Membrane cofactor protein (MCP; CD46) expression in transgenic mice.

Area of Science:

• Immunology
• Genetics
• Molecular Biology

Background:

• Human membrane cofactor protein (MCP; CD46) is a key complement regulator, widely distributed in humans.
• Mouse MCP expression is primarily in the testis, with a related protein (Crry) performing regulatory functions.
• Understanding MCP's role requires models that mimic human expression patterns.

Purpose of the Study:

• To develop mouse models expressing human MCP (CD46).
• To characterize the expression pattern and isoform distribution of human MCP in transgenic mice.
• To assess the utility of these mice for research into MCP function and disease.

Main Methods:

• Generation of transgenic mouse strains using YAC clones containing the human MCP gene.
• Immunohistochemistry, FACS, Western blotting, and RT-PCR to analyze MCP expression.
• Comparison of expression profiles between transgenic mice and human tissues.

Main Results:

• Three strains of transgenic mice expressing human MCP (CD46) were successfully generated.
• Expression levels varied with gene copy number, but isoform patterns and tissue distribution mirrored human expression.
• Tissue-specific isoform expression in kidney, salivary gland, and brain paralleled human patterns.
• Transgenic mice showed low-level expression on erythrocytes, similar to non-human primates.

Conclusions:

• Transgenic mice accurately replicate human MCP (CD46) expression patterns, including tissue-specific isoforms.
• These mice serve as a valuable tool for studying MCP's role in complement regulation, reproduction, and disease.
• The model facilitates research into infections and the function of MCP (CD46) in various physiological processes.