Claudin-12 is not required for blood-brain barrier tight junction function

Area of Science:

• Neuroscience
• Cell Biology
• Immunology

Background:

• The blood-brain barrier (BBB) maintains central nervous system (CNS) homeostasis by regulating molecular passage.
• Tight junctions (TJs), dominated by claudin-5, form a barrier in brain endothelial cells, preventing uncontrolled diffusion.
• While claudin-5 is key, other proteins likely contribute to BBB TJ complexes, prompting investigation into claudin-12's role.

Purpose of the Study:

• To investigate the expression and function of claudin-12 at the BBB.
• To determine claudin-12's role in BBB integrity during health and neuroinflammation.
• To conduct a comprehensive phenotypic analysis of claudin-12 deficient mice.

Main Methods:

• Generation of claudin-12-lacZ-knock-in C57BL/6J mice.
• Analysis of claudin-12 expression in various organs, including the CNS.
• Phenotypic screening of claudin-12 deficient mice in a multiple sclerosis model.

Main Results:

• Claudin-12 exhibits broad organ expression, with minimal presence in brain endothelium.
• Claudin-12 deficient mice show intact BBB integrity and no exacerbated neuroinflammation in a multiple sclerosis model.
• Precise claudin-12 localization at the BBB could not be determined due to antibody limitations.

Conclusions:

• Claudin-12 is not essential for establishing or maintaining BBB TJ integrity.
• Claudin-12 expression in cells lacking TJs suggests a non-classical TJ function.
• Phenotypic screening indicates potential roles for claudin-12 in neurological and cardiovascular functions.