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

Amino Acids. 2017 Mar;49(3):635-642. doi: 10.1007/s00726-016-2356-3. Epub 2016 Nov 18.

Abstract

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.

Keywords: Cornified cell envelope; Keratinocyte differentiation; Transglutaminase.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cell Differentiation
  • Embryo, Mammalian
  • Epidermis / growth & development
  • Epidermis / metabolism*
  • Epidermis / pathology
  • Filaggrin Proteins
  • GTP-Binding Proteins / deficiency
  • GTP-Binding Proteins / genetics*
  • Gene Expression
  • Heterozygote
  • Intermediate Filament Proteins / genetics
  • Intermediate Filament Proteins / metabolism
  • Keratin-1 / genetics
  • Keratin-1 / metabolism
  • Keratin-14 / genetics
  • Keratin-14 / metabolism
  • Keratinocytes / metabolism
  • Keratinocytes / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phenotype
  • Protein Glutamine gamma Glutamyltransferase 2
  • Protein Precursors / genetics
  • Protein Precursors / metabolism
  • Transglutaminases / deficiency
  • Transglutaminases / genetics*

Substances

  • Biomarkers
  • Filaggrin Proteins
  • Intermediate Filament Proteins
  • Keratin-1
  • Keratin-14
  • Krt14 protein, mouse
  • Protein Precursors
  • involucrin
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • transglutaminase 1
  • GTP-Binding Proteins