All Phenotypes Tuft1<tm1a(KOMP)Wtsi> MGI Mouse

decreased keratinocyte adhesion ( J:340887 )

• keratinocytes exhibit abnormal cell-cell contacts and impaired intermediate filament (IF) insertion to the desmosome

• intact but free-floating desmosomes without keratin attachment are seen close to the blister fluid, indicating their detachment from the IFs

• KRT5 staining showed a slight nuclear retraction, leaving wider gaps in between cells

waved hair ( J:340887 )

• all mice exhibit a woolly/wavy hair phenotype

abnormal hair shaft morphology ( J:340887 )

• hair displays a groove-like shape, unlike the flattened cylinder shape of wild-type hair

acantholysis ( J:340887 )

acanthosis ( J:340887 )

abnormal epidermis suprabasal layer morphology ( J:340887 )

• wounded skin shows a suprabasal split in the epidermis, with acantholysis and acanthosis

abnormal keratinocyte morphology ( J:340887 )

• keratinocytes exhibit keratin bundle retraction in the proximity of the nucleus

abnormal keratinocyte differentiation ( J:340887 )

• cultured keratinocytes show a significant downregulation of loriscrin and involucrin (late-stage differentiation markers) and an upregulation of desmoplakin, with predominant accumulation of desmoplakin in the cytoplasm

blistering ( J:340887 )

• spontaneous wounds exhibit blister fluid under a thick scab roof

skin lesions ( J:340887 )

• 40% of mice develop spontaneous skin erosions over time due to grooming, scratching and/or fighting, not observed in wild-type controls

increased pruritus ( J:340887 )

• first skin erosion outbursts appear to start a cascade of itching reactions that worsen the phenotype over time

• isolating affected mice or nail cutting does not improve animal welfare

decreased skin tensile strength ( J:340887 )

• 40% of mice develop a mild skin fragility phenotype