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

May 2014 in “ Journal of Biological Chemistry ”

David M. Alvarado, Pierre A. Coulombe

keratin keratin 5 keratin 8 KRT5 KRT8 intermediate filaments alopecia epidermal structure skin lesions cytoarchitecture hair loss skin structure

Studysummary In this study, targeting the expression of a keratin KRT5/KRT8 chimeric cDNA in keratin-deficient mice partially restored structural defects in epidermal cells, but did not fully normalize skin health. Our plain-language summary of this paper — not a Tressless recommendation.

The study explored the potential of a chimeric keratin protein, KRT8bc, to compensate for the absence of keratin 5 (Krt5) in mice, which is essential for skin integrity. Krt5-null mice, which usually experience severe skin fragility and neonatal lethality, were partially rescued by KRT8bc expression, with 47% surviving to adulthood. Despite forming intermediate filament bundles, KRT8bc could not fully replicate K5's functions, as evidenced by the development of alopecia and skin lesions in the rescued mice. The study highlighted the complexity of keratin protein interactions and the critical role of keratin IF self-organization in maintaining epidermal integrity.

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research Keratin Disorders: From Gene to Therapy

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This review discusses keratin disorders and potential RNA interference therapeutics, reporting no new clinical findings but highlighting the promise of siRNA for future treatments.

research Epidermolysis Bullosa Simplex: A Paradigm for Disorders of Tissue Fragility

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research Epidermal Abnormalities and Increased Malignancy of Skin Tumors in Human Epidermal Keratin 8-Expressing Transgenic Mice

49 citations , August 2004 in “The FASEB Journal”

This study found that transgenic mice expressing human keratin K8 in the epidermis showed increased progression of skin lesions toward malignancy, suggesting a role for K8 in the development of invasive skin cancer.

research The Functional Diversity of Epidermal Keratins Revealed by the Partial Rescue of the Keratin 14 Null Phenotype by Keratin 16

53 citations , September 1999 in “The journal of cell biology/The Journal of cell biology”

In this study, expressing human K16 in the epidermis of K14 null mice prevented early skin blistering but led to age-related anomalies, indicating K16 and K14 have distinct roles despite their sequence similarity.

research Onset of Keratin 17 Expression Coincides with the Definition of Major Epithelial Lineages During Skin Development

318 citations , October 1998 in “The Journal of Cell Biology”

This study found that ectopic expression of the lymphoid-enhancer factor can induce K17 protein in the skin, suggesting a link between skin development and wound repair processes in mice.

research Directed Expression of Keratin 16 to the Progenitor Basal Cells of Transgenic Mouse Skin Delays Skin Maturation

79 citations , August 1998 in “The Journal of Cell Biology”

In a transgenic mouse model, this study found that overexpression of keratin 16 in skin keratinocytes led to hyperkeratosis and increased EGF receptor signaling, altering skin cell behavior and structure.

research Increased Expression of Keratin 16 Causes Anomalies in Cytoarchitecture and Keratinization in Transgenic Mouse Skin

94 citations , October 1994 in “The Journal of Cell Biology”

This study demonstrates that overexpression of K16 in transgenic mice disrupts normal keratinization, leading to hyperkeratosis, acanthosis, and alterations in the skin's epithelial cells.

research The Structure of Human Trichohyalin: Potential Multiple Roles as a Functional EF-Hand-Like Calcium-Binding Protein, a Cornified Cell Envelope Precursor, and an Intermediate Filament-Associated (Cross-Linking) Protein

161 citations , June 1993 in “Journal of Biological Chemistry”

This study suggests that human trichohyalin may function as a flexible rod linking keratin intermediate filaments and as a scaffold protein in hair follicle and epidermis cell envelopes.