Analysis Tools
mortality/aging
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• double homozygous mice begin to die after 4 months of age and the median life span of females and males is reduced to 10 and 8 months, respectively, compared to about 22 months for wild-type
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cellular
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• after 14 weeks of selection with L-aspartic acid, N-(phosphonoacetyl) (PALA, an assay for gene amplification) homozygous MEFs develop resistance to up to 500uM PALA unlike wild-type cells which do not develop resistance and 20-fold greater than the resistance seen in Cdkn1a single homozygous MEFs
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• global mesangial proliferation involving 10 - 100% of glomeruli is seen in older double homozygotes
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• in some glomeruli
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• proliferation in response to cytokines is increased; however, T cell receptor independent proliferation is not increased compared to wild-type
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• low passage MEFs have a plating efficiency of up to 1.4% compared to 0.005% in wild-type cells, 0.025% in Gadd45a null cells, 1.6% in Trp53 null cells, and 1.2% in Cdkn1a null cells
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• global mesangial proliferation involving 10 - 100% of glomeruli is seen in older double homozygotes
• segmental glomerular endothelial cell proliferation is seen in older double homozygotes
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immune system
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• lymphoid hyperplasia is seen in the lymph nodes and spleen of 4 month old double homozygotes
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• at 7-9 months of age 73% of double homozygous females are leukopenic compared to 7% of wild-type mice and 47% of Gadd45a single homozygous females
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• at 7-9 months of age 53% of double homozygous females are lymphopenic compared to 7% of wild-type mice and 40% of Gadd45a single homozygous females
• at 7-9 months of age 46% of double homozygous males are lymphopenic
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• 2-fold increase in IgG1 and high levels of IgG2b and IgG3 anti-double stranded DNA antibodies at 7 - 9 months of age
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• 2-fold increase in IgM at 7 - 9 months of age
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• the sensitivity of primary T cell activation is increased with a 3- to 10-fold leftward shift in the dose-response curve and the maximal proliferative response is about 2-fold more than in wild-type cells
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• proliferation in response to cytokines is increased; however, T cell receptor independent proliferation is not increased compared to wild-type
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• after 4 months of age in female and male double homozygotes the occurrence and titer of antibodies against double stranded DNA is increased compared to wild-type mice and single homozygous mice
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• after 4 months of age in female and male double homozygotes the occurrence and titer of antibodies against histones is increased compared to wild-type mice and single homozygous mice
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• after 4 months of age in female and male double homozygotes the occurrence and titer of antibodies against single stranded DNA is increased compared to wild-type mice and single homozygous mice
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• lymphocytic infiltrates are seen in the lung and salivary glands at 4 months of age
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• some glomeruli contain inflammatory cells, nuclear debris, and mesangial cell interposition, mild dilation of the proximal tubules occurs, and mild to severe dense perivascular mononuclear cell infiltrates are seen suggesting autoimmune glomerulonphritis
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renal/urinary system
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• segmental endothelial cell proliferation is seen in older double homozygotes
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• global mesangial proliferation involving 10 - 100% of glomeruli is seen in older double homozygotes
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• in some glomeruli
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• global mesangial proliferation involving 10 - 100% of glomeruli is seen in older double homozygotes
• segmental glomerular endothelial cell proliferation is seen in older double homozygotes
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• 220 +/- 40 mg/dl of protein is seen in the urine of double homozygous mice suggesting chronic nephropathy
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• some glomeruli contain inflammatory cells, nuclear debris, and mesangial cell interposition, mild dilation of the proximal tubules occurs, and mild to severe dense perivascular mononuclear cell infiltrates are seen suggesting autoimmune glomerulonphritis
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• mild dilation of the proximal tubules
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homeostasis/metabolism
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• 220 +/- 40 mg/dl of protein is seen in the urine of double homozygous mice suggesting chronic nephropathy
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hematopoietic system
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• lymphoid hyperplasia is seen in the lymph nodes and spleen of 4 month old double homozygotes
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• at 7-9 months of age 73% of double homozygous females are leukopenic compared to 7% of wild-type mice and 47% of Gadd45a single homozygous females
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• at 7-9 months of age 53% of double homozygous females are lymphopenic compared to 7% of wild-type mice and 40% of Gadd45a single homozygous females
• at 7-9 months of age 46% of double homozygous males are lymphopenic
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• 2-fold increase in IgG1 and high levels of IgG2b and IgG3 anti-double stranded DNA antibodies at 7 - 9 months of age
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• 2-fold increase in IgM at 7 - 9 months of age
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• the sensitivity of primary T cell activation is increased with a 3- to 10-fold leftward shift in the dose-response curve and the maximal proliferative response is about 2-fold more than in wild-type cells
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• proliferation in response to cytokines is increased; however, T cell receptor independent proliferation is not increased compared to wild-type
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cardiovascular system
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• segmental endothelial cell proliferation is seen in older double homozygotes
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| systemic lupus erythematosus | DOID:9074 |
OMIM:152700 OMIM:300809 OMIM:605480 OMIM:608437 OMIM:609903 OMIM:609939 OMIM:610065 OMIM:610066 OMIM:612254 OMIM:612378 OMIM:613145 OMIM:614420 |
J:76041 | |
