Directed Expression of a Chimeric Type II Keratin Partially Rescues Keratin 5-null Mice

The study investigated the role of keratin intermediate filaments (IFs) in epidermal structure by expressing a chimeric KRT5/KRT8 cDNA (KRT8bc) in Krt5-null mice. The KRT8bc expression partially rescued the mice with a 47% success rate, while wild type KRT8 did not. This partial rescue was linked to lower than expected mRNA and protein levels of K8bc and K8. The K8bc was able to form IFs without K5, and electron microscopy showed partial restoration of keratin IF bundling and cytoarchitecture. However, KRT8bc replacement mice developed alopecia and skin lesions, indicating incomplete normalization of skin epithelia. The findings highlighted the importance of keratin IF self-organization and context-dependent regulation in maintaining epidermal structure.