reproductive system
• disorganization of seminiferous tubules with reduced proliferation index in degenerated testis regions at 3 months of age
• however, ratios of supporting (Sertoli) and interstitial (Leydig) cell populations appear normal
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• testicular degeneration, affecting >60% of the tissue, as early as 3 months after birth
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• acute inflammation detected in the surrounding connective tissue and epithelial component of epididymal tubules at 3 months of age, with increased recruitment of CD3e T-lymphocytes and F4/80 macrophages, and increased inflammatory cytokine expression relative to controls
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• distended tubular architecture with dramatic reduction of spermatozoa content in the epididymis lumen at 4 months of age
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• atrophic flattened cells and regions with squamous cell metaplasia in the epithelial component of epididymis
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• epididymis hypertrophy as early as 3 months after birth
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• epididymal fibrosis with large fibronectin, elastin and collagen deposits in the stromal epididymal component and a denser extacracellular matrix found at 3 months of age
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spermatocele
(
J:220689
)
• prominent spermatoceles in degenerated testis regions at 4 months of age
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• 90% of males are sterile
• however, typical meiosis I and II figures are observed
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• increased proliferation in the stroma and epithelium components of epididymal tissue, as shown by Ki67 staining
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• increased proliferating epididymis epithelial cells, as shown by Ki67 staining
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neoplasm
• following DMBA-TPA treatment mice develop an increased number of lesions relative to similarly-treated wild-type controls, with an average of 36 lesions/mouse vs 22 lesions/mouse at 20 weeks post-DMBA application
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• following DMBA-TPA treatment, 4% of neoplastic skin lesions (papillomas) progress to squamous cell carcinoma (SCC) relative to 0% (none) in wild-type controls
• malignant progression of papillomas correlates with decreased epidermal differentiation, associated with a significant downregulation of involucrin and a more modest reduction in loricrin and K1
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• onset of lesion formation is markedly accelerated with initial lesions appearing only 5 weeks post-DMBA application relative to >8 weeks in wild-type controls
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immune system
• increased inflammatory infiltration in DMBA-TPA induced papilloma lesions, with increased S100A8 mRNA levels relative to wild-type controls
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• acute inflammation detected in the surrounding connective tissue and epithelial component of epididymal tubules at 3 months of age, with increased recruitment of CD3e T-lymphocytes and F4/80 macrophages, and increased inflammatory cytokine expression relative to controls
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homeostasis/metabolism
• following DMBA-TPA treatment mice develop an increased number of lesions relative to similarly-treated wild-type controls, with an average of 36 lesions/mouse vs 22 lesions/mouse at 20 weeks post-DMBA application
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integument
• in vitro, primary keratinocytes from newborn homozygotes exhibit decreased protein levels of loricrin and suprabasal cytokeratins relative to controls
• however, no major changes in Ca2+ induced differentiation and cell adhesion to a collagen IV matrix are observed
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cellular
• in vitro, primary keratinocytes from newborn homozygotes exhibit decreased protein levels of loricrin and suprabasal cytokeratins relative to controls
• however, no major changes in Ca2+ induced differentiation and cell adhesion to a collagen IV matrix are observed
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endocrine/exocrine glands
• disorganization of seminiferous tubules with reduced proliferation index in degenerated testis regions at 3 months of age
• however, ratios of supporting (Sertoli) and interstitial (Leydig) cell populations appear normal
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• testicular degeneration, affecting >60% of the tissue, as early as 3 months after birth
|