Analysis Tools
reproductive system
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• Background Sensitivity: whereas a clearly penetrant (~50%), but variable, epididymal phenotype is first noted at 7 weeks of age on a congenic C57BL/6 background, similar epididymal lesions do not occur until late adulthood on a mixed background involving 129 and C57BL/6
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• at 7 weeks of age, 40% of male homozygotes show large spermatic granulomas characterized by breakdown of the tubule and resulting in a bolus of sperm, fluid and immune cells
• affected epididymides often show complete occlusion of the tubule resulting in severe tubule swelling upstream of the lesion and an absence of sperm in downstream tubules
• most spermatic granulomas are found in the cauda segment; however, lesions are occasionally noted in the caput and corpus segments
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• mutant epididymides exhibit absence of an intact epithelium and the presence of shed, free-floating cells consistent with a detached tubule epithelium
• other signs of epithelial breakdown include lymphocyte infiltration, vacuoles in the basal aspects of the epithelium, and epithelial metaplasia
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• Background Sensitivity: the variable, but highly penetrant (~89%) subfertility phenotype noted on a mixed genetic background appears to be reduced upon backcrossing the mutation onto a C57BL/6 congenic background
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cellular
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• when cultured on glass substrates lacking exogenous matrix, mutant primary epithelial-enriched epididymal cells produce 35% fewer islands than wild-type cells, despite an identical rate of epididymal epithelial cell proliferation
• however, cultures of both genotypes grown on exogenous recombinant substrates produce abundant epithelial islands while maintaining similar rates of proliferation, indicating that mutant epithelial epididymal cells display an intrinsic defect in cell adhesion
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immune system
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• at 7 weeks of age, 40% of male homozygotes show large spermatic granulomas characterized by breakdown of the tubule and resulting in a bolus of sperm, fluid and immune cells
• affected epididymides often show complete occlusion of the tubule resulting in severe tubule swelling upstream of the lesion and an absence of sperm in downstream tubules
• most spermatic granulomas are found in the cauda segment; however, lesions are occasionally noted in the caput and corpus segments
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