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The COL6A5-p.Glu2272* mutation induces chronic itch in mice
Ameer Abu Bakr Rasheed1, Marie-Christine Birling1,2, Giuseppe Lauria3
1Université de Strasbourg, CNRS, INSERM Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), 1 rue Laurent Fries, 67400, Illkirch, France.
Summary
A rare Collagen VI alpha 5 (COL6A5) gene variant causes chronic itch. This study developed a new mouse model that shows increased scratching and anxiety, offering insights into itch mechanisms.
Area of Science:
- Genetics
- Dermatology
- Neuroscience
Background:
- Chronic itch is a significant burden with complex causes.
- A specific Collagen VI alpha 5 (COL6A5) gene variant (p.Glu2272*) is linked to chronic neuropathic itch in patients.
- Reduced COL6A5 expression in skin was observed in affected patients.
Purpose of the Study:
- To develop and characterize the first mouse model for the COL6A5-p.Glu2272* mutation.
- To investigate the functional consequences of this mutation in vivo.
- To explore potential mechanisms linking COL6A5 to chronic itch.
Main Methods:
- CRISPR-Cas technology was used to create the COL6A5-p.Glu2272* mutant mouse model.
- RT-ddPCR was employed to measure mutant mRNA expression in dorsal root ganglia and skin.
- Phenotypic characterization included behavioral analysis (scratching, grooming, anxiety) and assessment of skin permeability.
Main Results:
- Mutant mice exhibited decreased COL6A5 mRNA levels in skin but normal levels in dorsal root ganglia.
- The mutation led to sex-specific dysmorphology and increased skin permeability.
- Mutant mice displayed elevated spontaneous scratching and grooming, with female mutants showing increased anxiety-like behavior.
Conclusions:
- The COL6A5-p.Glu2272* mutation contributes to chronic itch and associated behavioral changes in mice.
- This novel mouse model provides a valuable tool for elucidating the pathophysiology of COL6A5-related itch.
- The model may aid in identifying new therapeutic targets for chronic itch conditions.
