Transglutaminases are critically important enzymes in the assembly of the keratinocyte cornified envelope, as well as, structures of the hair follicle. It is clear that a particulate form of transglutaminase, TGK, is present in the skin and in the inner and outer root sheaths of the hair follicles; however, other enzymes possessing transglutaminase activity have also been identified in these structures. Because of this, distinguishing the contribution of each specific enzyme has been difficult. In addition, although transglutaminase function has been studied in cell culture models, these models do not faithfully reproduce in vivo differentiation. Transgenic TGk knockout mice would provide a unique system in which to study the function of TGk and to determine whether any of the known envelope precursors are selectively utilized by this enzyme in vivo. The availability of such mice would make it possible to study the effects of TGk deficiency on epidermal differentiation and disease and to assess its potential role during mouse development. The major goal of this Pilot and Feasibility Study is to develop TGk knockout mice.
Our specific aims are (1) to construct a plasmid that will permit us to inactivate the mouse TGk gene in mouse embryonic stem (ES) cells and (2) to establish TGk deficient ES cell lines and TGk deficient chimeric mice. To accomplish this goal, we will transfect cultured mouse embryonic stem (ES) cells with the TGk DNA- containing targeting vector, isolate TGk-deficient clonal cell lines and use these to generate chimeric and TGk-knockout mice.

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Case Western Reserve University
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Das, Lopa M; Binko, Amy M; Traylor, Zachary P et al. (2018) Defining the timing of 25(OH)D rescue following nitrogen mustard exposure. Cutan Ocul Toxicol 37:127-132
Griffith, Alexis D; Zaidi, Asifa K; Pietro, Ashley et al. (2018) A requirement for slc15a4 in imiquimod-induced systemic inflammation and psoriasiform inflammation in mice. Sci Rep 8:14451
Zaidi, Asifa K; Spaunhurst, Katrina; Sprockett, Daniel et al. (2018) Characterization of the facial microbiome in twins discordant for rosacea. Exp Dermatol 27:295-298
Bhaskaran, Natarajan; Liu, Zhihui; Saravanamuthu, Senthil S et al. (2018) Identification of Casz1 as a Regulatory Protein Controlling T Helper Cell Differentiation, Inflammation, and Immunity. Front Immunol 9:184
Mukherjee, Pranab K; Chandra, Jyotsna; Retuerto, Mauricio et al. (2018) Effect of alcohol-based hand rub on hand microbiome and hand skin health in hospitalized adult stem cell transplant patients: A pilot study. J Am Acad Dermatol 78:1218-1221.e5
Swindell, William R; Sarkar, Mrinal K; Liang, Yun et al. (2017) RNA-seq identifies a diminished differentiation gene signature in primary monolayer keratinocytes grown from lesional and uninvolved psoriatic skin. Sci Rep 7:18045
Mullin, Nathaniel K; Mallipeddi, Nikhil V; Hamburg-Shields, Emily et al. (2017) Wnt/?-catenin Signaling Pathway Regulates Specific lncRNAs That Impact Dermal Fibroblasts and Skin Fibrosis. Front Genet 8:183
Arbiser, Jack L; Nowak, Ron; Michaels, Kellie et al. (2017) Evidence for biochemical barrier restoration: Topical solenopsin analogs improve inflammation and acanthosis in the KC-Tie2 mouse model of psoriasis. Sci Rep 7:11198
Larkin, Emily; Hager, Christopher; Chandra, Jyotsna et al. (2017) The Emerging Pathogen Candida auris: Growth Phenotype, Virulence Factors, Activity of Antifungals, and Effect of SCY-078, a Novel Glucan Synthesis Inhibitor, on Growth Morphology and Biofilm Formation. Antimicrob Agents Chemother 61:
Hutnick, Melanie A; Ahsanuddin, Sayeeda; Guan, Linna et al. (2017) PEGylated Dendrimers as Drug Delivery Vehicles for the Photosensitizer Silicon Phthalocyanine Pc 4 for Candidal Infections. Biomacromolecules 18:379-385

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