Add like
Add dislike
Add to saved papers

Investigations into the filaggrin null phenotype: showcasing the methodology for CRISPR/Cas9 editing of human keratinocytes.

Ever since the association between filaggrin (FLG) loss-of-function mutations and ichthyosis vulgaris and atopic dermatitis disease onset was identified, filaggrins function has been under investigation. Intra-individual genomic predisposition, immunological confounders, and environmental interactions complicate the comparison between FLG genotypes and related causal effects. Using CRISPR/Cas9, we generated human FLG knockout (ΔFLG) N/TERT-2G keratinocytes. Filaggrin deficiency was demonstrated by immunohistochemistry of human epidermal equivalent (HEE) cultures. Next to (partial) loss of structural proteins (IVL, HRNR, KRT2, and TGM1), the stratum corneum was more dense and lacked the typical basket weave appearance. In addition, electrical impedance spectroscopy and transepidermal water loss analyses highlighted a compromised epidermal barrier in ΔFLG-HEEs. Correction of FLG reinstated the presence of keratohyalin granules in the stratum granulosum, filaggrin protein expression, and expression of aforementioned proteins. The beneficial effects on stratum corneum formation were reflected by normalization of EIS and TEWL. This study demonstrates the causal phenotypical and functional consequences of filaggrin deficiency, indicating filaggrin is not only central in epidermal barrier function but also vital for epidermal differentiation by orchestrating the expression of other important epidermal proteins. These observations pave the way to fundamental investigations into the exact role of filaggrin in skin biology and disease.

Full text links

We have located links that may give you full text access.
Can't access the paper?
Try logging in through your university/institutional subscription. For a smoother one-click institutional access experience, please use our mobile app.

For the best experience, use the Read mobile app

Mobile app image

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app

All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

By using this service, you agree to our terms of use and privacy policy.

Your Privacy Choices Toggle icon

You can now claim free CME credits for this literature searchClaim now

Get seemless 1-tap access through your institution/university

For the best experience, use the Read mobile app