Varying phenotypes in swine versus murine transgenic models constitutively expressing the same human Sonic hedgehog transcriptional activator, K5-HGLI2ΔN
| Autor: | Amy C. McCalla-Martin, Jose L. Estrada, Keith E. Linder, Xiaoxin Chen, Jorge A. Piedrahita |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Pathology medicine.medical_specialty Swine Somatic cell Recombinant Fusion Proteins Transgene Sus scrofa Kruppel-Like Transcription Factors Acanthosis Zinc Finger Protein Gli2 Animals Genetically Modified Mice Species Specificity GLI2 Gene expression Genetics medicine Animals Humans Genetic Predisposition to Disease Basal cell carcinoma Transgenes Skin Diseases Infectious Sonic hedgehog Hedgehog integumentary system biology Nuclear Proteins Fibroblasts medicine.disease Animals Suckling Phenotype Pyoderma Immunology biology.protein Keratins Female Animal Science and Zoology Epidermis Hair Follicle Agronomy and Crop Science Biotechnology |
| Zdroj: | Transgenic Research. 19:869-887 |
| ISSN: | 1573-9368 0962-8819 |
| DOI: | 10.1007/s11248-010-9362-0 |
| Popis: | This study was undertaken to characterize the effects of constitutive expression of the hedgehog transcriptional activator, Gli2, in porcine skin. The keratinocyte-specific human transgene, K5-hGli2 Delta N, was used to produce transgenic porcine lines via somatic cell nuclear transfer techniques. In mice, K5-hGli2 Delta N induces epithelial downgrowths resembling basal cell carcinomas. Our porcine model also developed these basal cell carcinoma-like lesions, however gross tumor development was not appreciated. In contrast to the murine model, diffuse epidermal changes as well as susceptibility to cutaneous infections were seen in the swine model. Histologic analysis of transgenic piglets revealed generalized epidermal changes including: epidermal hyperplasia (acanthosis), elongated rete ridges, parakeratotic hyperkeratosis, epidermal neutrophilic infiltration, capillary loop dilation and hypogranulosis. By 2 weeks of age, the transgenic piglets developed erythematic and edematous lesions at high contact epidermal areas and extensor surfaces of distal limb joints. Despite antibiotic treatment, these lesions progressed to a deep bacterial pyoderma and pigs died or were euthanized within weeks of birth. Non-transgenic littermates were phenotypically normal by gross and histological analysis. In summary, constitutive expression of the human hGli2 Delta N in keratinocytes, results in cutaneous changes that have not been reported in the K5-hGli2 Delta N murine model. These findings indicate a need for a multiple species animal model approach in order to better understand the role of Gli2 in mammalian skin. |
| Databáze: | OpenAIRE |
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