Literature review reveals phenotypic and molecular characteristics of CMT2A mammalian models, highlighting translational challenges in developing targeted therapies.
Key Points
To review the development, phenotypic characteristics, and limitations of mammalian in vivo models of Charcot-Marie-Tooth type 2A (CMT2A) to guide translational therapeutic strategies.
Reviewed published literature on in vivo experimental systems of CMT2A associated with Mitofusin 2 (MFN2) gene mutations, focusing predominantly on murine models.
Assessed models based on phenotypic, histopathological, and molecular features affecting mitochondrial fusion, fission, mitophagy, and axonal transport.
Murine models successfully recreate core molecular deficits of CMT2A, including disrupted mitochondrial dynamics, impaired axonal trafficking, and altered mitophagy.
Existing models display variable phenotypic penetrance and histopathological severity, presenting distinct translational limitations for testing candidate treatments intended for clinical use.