Mouse Models of Human Proprotein Convertase Insufficiency

Area of Science:

• Biochemistry
• Molecular Biology
• Genetics

Background:

• Proprotein convertases (PCs) are essential enzymes involved in post-translational modification.
• The kexin-like subfamily of PCs plays a critical role in processing various peptide precursors.

Purpose of the Study:

• To provide a comprehensive review of kexin-like proprotein convertase structure, biochemistry, and function.
• To summarize human insufficiency syndromes and compare findings with animal models.
• To discuss the utility and limitations of mouse models in understanding PC roles in disease.

Main Methods:

• Review of existing literature on proprotein convertase structure, biochemistry, and function.
• Analysis of human proprotein convertase insufficiency syndromes and polymorphisms.
• Comparison of human data with findings from convertase null and mutant mouse models.

Main Results:

• Mouse models have elucidated specific convertase functions and identified novel substrates, such as procorin for PACE4 in the heart.
• Despite limitations like species-specific differences and functional redundancy, knockout mouse models have substantially improved understanding of PC roles.
• Specific models (furin, PC1/3, PC5/6) highlight the value of these models in studying human diseases.

Conclusions:

• Kexin-like proprotein convertases are vital for producing diverse bioactive peptides and proteins.
• Mouse models, particularly sophisticated ones, are invaluable tools for dissecting PC functions and their implications in human health and disease.
• Further development of advanced mouse models may support therapeutic strategies targeting convertase activity.