Amino Acids

, Volume 49, Issue 3, pp 635–642 | Cite as

Characterization of TG2 and TG1–TG2 double knock-out mouse epidermis

  • Consuelo Pitolli
  • Valentina Pietroni
  • Lyuben Marekov
  • Alessandro Terrinoni
  • Kiyofumi Yamanishi
  • Cinzia Mazzanti
  • Gerry Melino
  • Eleonora Candi
Original Article


Transglutaminases (TGs) are a family of enzymes that catalyse the formation of isopeptide bonds between the γ-carboxamide groups of glutamine residues and the ε-amino groups of lysine residues leading to cross-linking reactions among proteins. Four members, TG1, TG2, TG3, and TG5, of the nine mammalian enzymes are expressed in the skin. TG1, TG3 and TG5 crosslinking properties are fundamental for cornified envelope assembly. In contrast, the role of TG2 in keratinization has never been studied at biochemical level in vivo. In this study, taking advantage of the TG2 knock-out (KO) and TG1 heterozygous mice, we generated and characterized the epidermis of TG1–TG2 double knock-out (DKO) mice. We performed morphological analysis of the epidermis and evaluation of the expression of differentiation markers. In addition, we performed analysis of the amino acid composition from isolated corneocytes. We found a significant change in amino acid composition in TG1KO cornified cell envelopes (CEs) while TG2KO amino acid composition was similar to wild-type CEs. Our results confirm a key role of TG1 in skin differentiation and CE assembly and demonstrate that TG2 is not essential for CE assembly and skin formation.


Keratinocyte differentiation Cornified cell envelope Transglutaminase 





Extracellular matrix


Knock-out mouse


Double knock-out mouse


Cornified cell envelope



This work was mainly supported by “Ricerca Corrente RC-1” Italian Ministry of Health to AT, and partially supported by the Medical Research Council (MRC), “Fondazione Roma” NCD Grant to GM and EC.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  • Consuelo Pitolli
    • 1
  • Valentina Pietroni
    • 1
  • Lyuben Marekov
    • 2
  • Alessandro Terrinoni
    • 3
  • Kiyofumi Yamanishi
    • 4
  • Cinzia Mazzanti
    • 3
  • Gerry Melino
    • 1
  • Eleonora Candi
    • 1
    • 3
  1. 1.Department of Experimental Medicine and SurgeryUniversity of Rome “Tor Vergata”RomeItaly
  2. 2.National Institutes of HealthBethesdaUSA
  3. 3.Biochemistry LaboratoryIDI-IRCCSRomeItaly
  4. 4.Department of DermatologyHyogo College of MedicineNishinomiyaJapan

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