[Genetically modified animal models in cardiovascular research].

Area of Science:

• Molecular Medicine
• Cardiovascular Biology
• Genetics

Context:

• Cellular and organ function are fundamentally determined by their specific protein complements.
• Alterations in protein pools are observed during normal development and in various pathologies, particularly in the heart.
• Congenital heart diseases exhibit distinct shifts in cardiac motor proteins.

Purpose:

• To establish models for studying pathogenic processes longitudinally by directing the heart to stably synthesize candidate proteins.
• To determine if a protein's presence directly or indirectly causes observed effects, aiming to identify potential therapeutic targets.
• To understand the mechanism and function of different mutated proteins and protein isoforms by precisely altering the heart's protein complement.

Summary:

• Gene targeting and transgenesis in mice enable modification of the mammalian genome and cardiac motor protein complement.
• Directing engineered protein expression to the heart allows for remodeling of the cardiac protein profile.
• This enables the study of consequences of single genetic manipulations at multiple biological levels under normal and stress conditions.

Impact:

• Provides a method to establish both mechanism and function of different mutated proteins and protein isoforms.
• Facilitates the study of molecular, biochemical, cytological, and physiological consequences of genetic manipulation in the heart.
• Aids in defining potential therapeutic targets for heart conditions by elucidating protein function in disease models.