In vivo effects of inducible transgene expression of the age-associated glycogenes St6gal1 and Man1a on epidermal homeostasis

Inducible epidermal expression of St6gal1 and Man1a in mice alters epidermal homeostasis, with Man1a induction reducing epidermal proliferation and thickness and St6gal1 induction driving skin inflammation.

• Why it matters: Aging skin shows higher a2,6-sialylated N-glycans and upregulated glycogenes, but their in vivo functional roles in epidermal maintenance and inflammation are unclear.
• What they did: Doxycycline-inducible transgenic mice were generated with ubiquitous or epidermis-specific drivers expressing St6gal1 and/or Man1a; lectin assays (SNA, rHeltuba) confirmed glycosylation changes, and SNA pull-down plus mass spectrometry identified candidate a2,6-sialylated proteins.
• The result: Man1a induction reduced epidermal proliferation and thickness, while St6gal1 induction caused splenomegaly and elevated inflammatory signature genes in skin without measurable epidermal proliferation or morphology changes; combined transgenes produced a hybrid phenotype dependent on epidermal expression.

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