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Dermatopathology
Volume 12
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10.3390/dermatopathology12030030
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Article

Mimicking the LOX-Related Autosomal Recessive Congenital Ichthyosis Skin Disease Using a CRISPR-Cas9 System and Unravelling 12S-LOX Function in the Skin

by
Carolyne Simard-Bisson
1,
Sébastien Larochelle
1,
Véronique J. Moulin
1,2,*,† and
Bernard Fruteau de Laclos
1,3,†
1
Centre de Recherche du CHU de Québec-Université Laval and Centre de Recherche en Organogénèse Expérimentale de l’Université Laval/LOEX, Quebec, QC G1J 1Z4, Canada
2
Department of Surgery, Faculty of Medicine, Université Laval, Quebec, QC G1V 0A6, Canada
3
Department of Molecular Biology, Medical Biochemistry and Pathology, Faculty of Medicine, Université Laval, Quebec, QC G1V 0A6, Canada
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Dermatopathology 2025, 12(3), 30; https://doi.org/10.3390/dermatopathology12030030
Submission received: 15 July 2025 / Revised: 29 August 2025 / Accepted: 5 September 2025 / Published: 11 September 2025
(This article belongs to the Section Experimental Dermatopathology)
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Abstract

Stratum Corneum (SC) formation in the human epidermis requires lipid processing. Lipoxygenases (LOXs) such as 12R-Lipoxygenase (12R-LOX) and Epidermis-type lipoxygenase 3 (eLOX-3) contribute to this process. Mutations in their genes cause Autosomal Recessive Congenital Ichthyosis (ARCI) in patients. On the other hand, 12S-lipoxygenase (12S-LOX) is expressed in the human epidermis, but its role still remains to be clarified. The involvement of eLOX-3, 12R, and 12S-LOX in conditions or processes such as skin photodamage, wound healing, psoriasis, and atopic dermatitis is suggested but still remains unclear. In order to eventually gain a better understanding of the role of these LOXs in such processes, models of Tissue-Engineered Skins (TESs) with an impaired expression for the native form of either eLOX-3, 12R-LOX, or 12S-LOX were produced using CRISPR-Cas9(D10A) technology. All three models showed impaired keratinocyte differentiation and changes in the prevalence or the size of lipid droplets within the most superficial layers, thus reproducing features observed in ARCI and supporting a role for 12S-LOX in SC formation. Since eLOX-3 and 12R-LOX depleted TES’s reproduced features observed in ARCI, such models can be considered as reliable tools for the functional studies of these LOXs in the human epidermis.
Keywords: epidermis; keratinocytes; lipoxygenase; tissue engineering; CRISPR-Cas9 systems epidermis; keratinocytes; lipoxygenase; tissue engineering; CRISPR-Cas9 systems

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MDPI and ACS Style

Simard-Bisson, C.; Larochelle, S.; Moulin, V.J.; Fruteau de Laclos, B. Mimicking the LOX-Related Autosomal Recessive Congenital Ichthyosis Skin Disease Using a CRISPR-Cas9 System and Unravelling 12S-LOX Function in the Skin. Dermatopathology 2025, 12, 30. https://doi.org/10.3390/dermatopathology12030030

AMA Style

Simard-Bisson C, Larochelle S, Moulin VJ, Fruteau de Laclos B. Mimicking the LOX-Related Autosomal Recessive Congenital Ichthyosis Skin Disease Using a CRISPR-Cas9 System and Unravelling 12S-LOX Function in the Skin. Dermatopathology. 2025; 12(3):30. https://doi.org/10.3390/dermatopathology12030030

Chicago/Turabian Style

Simard-Bisson, Carolyne, Sébastien Larochelle, Véronique J. Moulin, and Bernard Fruteau de Laclos. 2025. "Mimicking the LOX-Related Autosomal Recessive Congenital Ichthyosis Skin Disease Using a CRISPR-Cas9 System and Unravelling 12S-LOX Function in the Skin" Dermatopathology 12, no. 3: 30. https://doi.org/10.3390/dermatopathology12030030

APA Style

Simard-Bisson, C., Larochelle, S., Moulin, V. J., & Fruteau de Laclos, B. (2025). Mimicking the LOX-Related Autosomal Recessive Congenital Ichthyosis Skin Disease Using a CRISPR-Cas9 System and Unravelling 12S-LOX Function in the Skin. Dermatopathology, 12(3), 30. https://doi.org/10.3390/dermatopathology12030030

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