Archives of Dermatological Research

, Volume 304, Issue 5, pp 377–386 | Cite as

Ichthyin/NIPAL4 localizes to keratins and desmosomes in epidermis and Ichthyin mutations affect epidermal lipid metabolism

  • Johanna Dahlqvist
  • Gunilla T. Westermark
  • Anders Vahlquist
  • Niklas DahlEmail author
Original Paper


Autosomal recessive congenital ichthyosis (ARCI) is a group of disorders characterized by abnormal desquamation of the skin and a disrupted epidermal water barrier. Ichthyin/NIPAL4 gene mutations have been identified in a subgroup of ARCI patients, but the role of ichthyin in epidermis remains elusive. In order to obtain new insights concerning the characteristics of ichthyin and the ARCI pathogenesis, we studied the expression and localization of ichthyin and related epidermal components in cultured keratinocytes and skin sections from patients with Ichthyin mutations and healthy controls. We observed an up-regulation of Ichthyin mRNA levels after in vitro differentiation of keratinocytes from both a patient with Ichthyin mutations and controls. Confocal and electron microscopy analyses of immunolabeled skin sections revealed that ichthyin localizes to desmosomes and keratins in both patients with mutant Ichthyin and controls, with an increased immunolabeling in patients. Nile red lipid analysis of skin sections exposed intra-cellular lipid accumulations in cells of the granular and cornified layers in patients but not in controls, consistent with the pathognomonic lipid membrane structures previously identified in epidermis from patients. Our combined findings indicate that ichthyin is associated with keratins and desmosomes in epidermis and is involved in lipid metabolism, possibly through processing of lamellar bodies. These results provide new clues to the understanding of the epidermal water barrier and the pathogenesis in ARCI.


Autosomal recessive ichthyosis Ichthyin/NIPAL4 Epidermal expression Localization Lipid metabolism 



We thank Dr Hans Törmä and Dr Casimiro Castillejo-Lopez for fruitful discussions and for providing antibodies and Dr Ingrid Hausser for valuable comments. We acknowledge Inger Pihl-Lundin for immunohistochemical work and Hao Li for technical support. This work was supported by the Swedish Research Council (K2010-66X-10829-17-3 to N.D. and K2010-55X-20326-04-03 to G.T.W.), Uppsala University, Science for Life Laboratory and Uppsala University Hospital.

Supplementary material

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Supplementary material 1 (PDF 11268 kb)


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Johanna Dahlqvist
    • 1
  • Gunilla T. Westermark
    • 2
  • Anders Vahlquist
    • 3
  • Niklas Dahl
    • 1
    Email author
  1. 1.Department of Immunology, Genetics and Pathology, Science for Life LaboratoryUppsala UniversityUppsalaSweden
  2. 2.Department of Medical Cell BiologyUppsala UniversityUppsalaSweden
  3. 3.Department of Medical SciencesUppsala University HospitalUppsalaSweden

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