Analysis Tools
mortality/aging
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• mice have a considerably shorter life span than wild-type controls
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cellular
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• following apoptotic induction with TNF and cycloheximide, MEFs show a delay in apoptotic DNA degradation relative to wild-type MEFs (time for 50% of apoptotic nuclei turnover is >48 hrs vs 24 hrs, respectively)
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• primary MEFs exhibit significantly decreased cell survival following exposure to mitomycin C
• in response to the DNA-damaging agents methylmethanesulfonate and mitomycin C or UV radiation, the number of TUNEL+ MEFs undergoing apoptosis is 3-4 times higher than that in wild-type MEFs
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• primary MEFs exhibit significantly decreased cell survival following exposure to methylmethanesulfonate
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• mice show accumulation of TUNEL+ nuclei in kidney tissues, unlike wild-type controls (83.3 vs 10.3 TUNEL+ nuclei per view, respectively)
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• mice show accumulation of TUNEL+ nuclei in lung tissues, unlike wild-type controls (33.0 vs 0.5 TUNEL+ nuclei per view, respectively)
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• primary MEFs show ~26-fold higher spontaneous mutation rate than wild-type MEFs, as determined by an Hprt mutant assay
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immune system
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• in 35% cases, large cluster or sheet-like plasma cells are seen in the interfollicular region
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• mice develop a lymphoproliferative phenotype, characterized by marked follicular and interfollicular hyperplasia
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• mice develop autoimmunity and a lymphoproliferative disorder by 9-12 months of age
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• at 9-12 months of age, the serum anti-nuclear antigen antibody levels are 1.51 +/- 0.6 unit/ul relative to 0.35 +/- 0.3 unit/ul in wild-type mice
• CLIFT analysis revealed that antibodies to nuclear antigens present in sera are against dsDNA
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• at 9-12 months of age, the serum levels of anti-double stranded DNA antibodies are significantly higher than in wild-type controls
• DNA-IgG complex abundance is 2-3-fold higher than that in wild-type sera
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• at 9-12 months of age, 58% of mice develop chronic lung inflammation relative to 19% of age-matched wild-type mice
• at >6 months of age, a significantly higher number of mice develop chronic subcutaneous inflammation around the external urogenital area than wild-type controls
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• mice show deposition of IgG-C3 immune complexes onto the glomeruli and capillary walls of the kidneys
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• at 9-12 months of age, 58% of mice develop chronic lung inflammation relative to 19% of age-matched wild-type mice
• deposition of IgG-C3 immune complexes onto cells in the lungs
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• mice develop pulmonary interstitial inflammation characterized by pneumonocyte hyperplasia and accumulation of inflammatory cells, including significant lymphoplasmacytic infiltrate
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neoplasm
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• at 14-20 months of age, 6.5% of mice develop malignant tumors in the liver, unlike wild-type controls
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• at 14-20 months of age, 61.2% of mice develop lung adenoma relative to 17.6% of age-matched wild-type mice
• of the 38 mice with lung adenoma, 58% had one tumor, 21% had two tumors and 21% had three or more tumors
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• at 14-20 months of age, 12% of mice develop lung adenocarcinoma associated with marked chronic inflammation, whereas only 1.9% of wild-type mice develop a malignant lung tumor
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• at 14-20 months of age, 8.1% of mice develop malignant tumors in the testis or ovary, unlike wild-type controls
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hematopoietic system
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• mice develop striking extrameduallry hematopoiesis
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• in 35% cases, large cluster or sheet-like plasma cells are seen in the interfollicular region
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respiratory system
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• mice show accumulation of TUNEL+ nuclei in lung tissues, unlike wild-type controls (33.0 vs 0.5 TUNEL+ nuclei per view, respectively)
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• at 9-12 months of age, 58% of mice develop chronic lung inflammation relative to 19% of age-matched wild-type mice
• deposition of IgG-C3 immune complexes onto cells in the lungs
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• mice develop pulmonary interstitial inflammation characterized by pneumonocyte hyperplasia and accumulation of inflammatory cells, including significant lymphoplasmacytic infiltrate
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• at 14-20 months of age, 61.2% of mice develop lung adenoma relative to 17.6% of age-matched wild-type mice
• of the 38 mice with lung adenoma, 58% had one tumor, 21% had two tumors and 21% had three or more tumors
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• at 14-20 months of age, 12% of mice develop lung adenocarcinoma associated with marked chronic inflammation, whereas only 1.9% of wild-type mice develop a malignant lung tumor
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renal/urinary system
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• mice show accumulation of TUNEL+ nuclei in kidney tissues, unlike wild-type controls (83.3 vs 10.3 TUNEL+ nuclei per view, respectively)
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• mice show deposition of IgG-C3 immune complexes onto the glomeruli and capillary walls of the kidneys
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reproductive system
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• at 14-20 months of age, 8.1% of mice develop malignant tumors in the testis or ovary, unlike wild-type controls
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liver/biliary system
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• at 14-20 months of age, 6.5% of mice develop malignant tumors in the liver, unlike wild-type controls
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growth/size/body
