22. Koch PJ, de Viragh PA, Scharer E, Bundman D, Longley MA, et al. (2000) Lessons from loricrin-deficient mice: compensatory mechanisms maintaining skin barrier function in the absence of a major cornified envelope protein. J Cell Biol 151(2): 389–400. 23. O’Keefe EJ, Hamilton EH, Lee SC, Steinert P (1993) Trichohyalin: a structural protein of hair, tongue, nail, and epidermis. J Invest Dermatol 101(1 Suppl): 65S–71S. 24. Steinert PM, Parry DA, Marekov LN (2003) Trichohyalin mechanically strengthens the hair follicle: multiple cross-bridging roles in the inner root sheath. J Biol Chem 278(42): 41409–19. 25. Tarcsa E, Marekov LN, Andreoli J, Idler WW, Candi E, et al. (1997) The fate of trichohyalin. Sequential post-translational modifications by peptidyl-arginine deiminase and transglutaminases. J Biol Chem 272(44): 27893–901. 26. Zhang J, Zhi HY, Ding F, Luo AP, Liu ZH (2005) Transglutaminase 3 expression in C57BL/6J mouse embryo epidermis and the correlation with its differentiation. Cell Res 15(2): 105–10. 27. Inada R, Matsuki M, Yamada K, Morishima Y, Shen SC, et al. (2000) Facilitated wound healing by activation of the Transglutaminase 1 gene. Am J Pathol 157(6): 1875–82. 28. Verderio EA, Johnson TS, Griffin M (2005) Transglutaminases in wound healing and inflammation. Prog Exp Tumor Res 38: 89–114. 29. Stephens P, Grenard P, Aeschlimann P, Langley M, Blain E, et al. (2004) Crosslinking and G-protein functions of transglutaminase 2 contribute differentially to fibroblast wound healing responses. J Cell Sci 117(Pt 15): 3389–403. 30. Siegel M, Strnad P, Watts RE, Choi K, Jabri B, et al. (2008) Extracellular transglutaminase 2 is catalytically inactive, but is transiently activated upon tissue injury. PLoS One 3(3): e1861. 31. Grenard P, Bates MK, Aeschlimann D (2001) Evolution of transglutaminase genes: identification of a transglutaminase gene cluster on human chromosome 15q15. Structure of the gene encoding transglutaminase X and a novel gene family member, transglutaminase Z. J Biol Chem 276(35): 33066–78. 32. Sevilla LM, Nachat R, Groot KR, Klement JF, Uitto J, et al. (2007) Mice deficient in involucrin, envoplakin, and periplakin have a defective epidermal barrier. J Cell Biol 179(7): 1599–612. 33. Hardman MJ, Sisi P, Banbury DN, Byrne C (1998) Patterned acquisition of skin barrier function during development. Development 125(8): 1541–52. 34. Yamada K, Matsuki M, Morishima Y, Ueda E, Tabata K, et al. (1997) Activation of the human transglutaminase 1 promoter in transgenic mice: terminal differentiation-specific expression of the TGM1-lacZ transgene in keratinized stratified squamous epithelia. Hum Mol Genet 6(13): 2223–31. 35. Yamane A, Fukui M, Sugimura Y, Itoh M, Alea MP, et al. (2010) Identification of a preferred substrate peptide for transglutaminase 3 and detection of in situ activity in skin and hair follicles. FEBS J 277(17): 3564–74. 36. Lee SC, Kim IG, Marekov LN, O’Keefe EJ, Parry DA, et al. (1993) The structure of human trichohyalin. Potential multiple roles as a functional EF- hand-like calcium-binding protein, a cornified cell envelope precursor, and an intermediate filament-associated (cross-linking) protein. J Biol Chem 268(16): 12164–76. 37. Steinert PM, Kartasova T, Marekov LN (1998) Biochemical evidence that small proline-rich proteins and trichohyalin function in epithelia by modulation of the In vivo Role of TGase 3 biomechanical properties of their cornified cell envelopes. J Biol Chem 273(19): 11758–69. 38. Buxman MM, Wuepper KD (1975) Keratin cross-linking and epidermal transglutaminase. A review with observations on the histochemical and immunochemical localization of the enzyme. J Invest Dermatol 65(1): 107–112. 39. Candi E, Tarcsa E (1998) A highly conserved lysine residue on the head domain of type II keratins is essential for the attachment of keratin intermediate filaments to the cornified cell envelope through isopeptide crosslinking by transglutaminases. Proc Natl Acad Sci U S A 95(5): 2067–72. 40. Thibaut S, Candi E, Pietroni V, Melino G, Schmidt R, et al. (2005) Transglutaminase 5 expression in human hair follicle. J Invest Dermatol 125(3): 581–5. 41. Lee YJ, Rice RH, Lee YM (2006) Proteome analysis of human hair shaft: from protein identification to posttranslational modification. Mol Cell Proteomics 5(5): 789–800. 42. Wang Z, Wong P, Langbein L, Schweizer J, Coulombe PA (2003) Type II epithelial keratin 6hf (K6hf) is expressed in the companion layer, matrix, and medulla in anagen-stage hair follicles. J Invest Dermatol 121(6): 1276–82. 43. McGowan KM, Coulombe PA (1998) Onset of keratin 17 expression coincides with the definition of major epithelial lineages during skin development. J Cell Biol 143(2): 469–86. 44. McGowan KM, Tong X, Colucci-Guyon E, Langa F, Babinet C, et al. (2002) Keratin 17 mice exhibit age- and strain-dependent alopecia. Genes Dev 16(11): 1412–22. 45. McLean WH, Rugg EL, Lunny DP, Morley SM, Lane EB, et al. (1995) Keratin 16 and keratin 17 mutations cause pachyonychia congenita. Nat Genet 9(3): 273–8. 46. Clementi M, Cardin de Stefani E, Dei Rossi C, Avventi V, Tenconi R (1986) Pachyonychia congenita Jackson-Lawler type: a distinct malformation syn- drome. Br J Dermatol 114(3): 367–70. 47. Appel B, Messina SJ (1942) Pili torti hereditaria. N Engl J Med 226: 912–915. 48. Medland SE, Nyholt DR, Painter JN, McEvoy BP, McRae AF, et al. (2009) Common variants in the trichohyalin gene are associated with straight hair in Europeans. Am J Hum Genet 85(5): 750–755. 49. Rice RH, Wong VJ, Price VH, Hohl D, Pinkerton KE (1996) Cuticle cell defects in lamellar ichthyosis hair and anomalous hair shaft syndromes visualized after detergent extraction. Anat Rec 246(4): 433–40. 50. Kuramoto N, Takizawa T, Takizawa T, Matsuki M, Morioka H, et al. (2002) Development of ichthyosiform skin compensates for defective permeability barrier function in mice lacking transglutaminase 1. J Clin Invest 109(2): 243–50. 51. Bowness JM, Tarr AH, Wong T (1988) Increased transglutaminase activity during skin wound healing in rats. Biochim Biophys Acta 967(2): 234–40. 52. Nunes I, Gleizes PE, Metz CN, Rifkin DB (1997) Latent transforming growth factor-beta binding protein domains involved in activation and transglutamin- ase-dependent cross-linking of latent transforming growth factor-beta. J Cell Biol 136(5): 1151–63. 53. Akimov SS, Krylov D, Fleischman LF, Belkin AM (2000) Tissue transgluta- minase is an integrin-binding adhesion coreceptor for fibronectin. J Cell Biol 148(4): 825–38. 54. Haroon ZA, Hettasch JM, Lai TS, Dewhirst MW, Greenberg CS (1999) Tissue transglutaminase is expressed, active, and directly involved in rat dermal wound healing and angiogenesis. FASEB J 13(13): 1787–95. PLoS ONE | www.plosone.org 12 April 2012 | Volume 7 | Issue 4 | e34252