Analysis Tools
mortality/aging
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• mice show a reduced life span, with losses as early as 6 weeks of age
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cardiovascular system
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• 87.5% of euthanized mice show chronic passive congestion of the liver
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• hearts of clinically healthy mice show variously sized regions of pallor
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• 87.5% of euthanized mice show atrial dilation
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• hearts of clinically healthy mice are often mildly to markedly enlarged
• 87.5% of euthanized mice show markedly enlarged hearts
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• hearts of clinically healthy mice often show right or biventricular dilation
• 87.5% of euthanized mice show ventricular dilation
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• severe vasculitis in both large- and small-caliber vessels at 6 months of age, characterized by influx of inflammatory cells, medial necrosis, and disruption of the vessel wall by protein-rich deposits
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• 87.5% of euthanized mice exhibit congestive heart failure characterized by bicavitary effusions
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immune system
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• increased B220+ B cell numbers in spleen
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• increased CD138+ plasma cell numbers in spleen
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• increased number of CD4+ T cells in spleen
• however, the number of splenic CD8+ T cells is normal
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• increased regulatory T cell number in spleen
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• significantly increased total serum IgG levels
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• both CD4+ and CD8+ splenocytes show up-regulated expression of the activation marker CD69
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• secondary lymphoid organs show expanded lymphoid follicles and increased numbers of germinal centers at 6 months of age
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• enlarged spleens as early as 4 months of age
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• significantly increased spleen weight at 4 and 6 months of age
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• increased splenic nucleated cell count
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• lymph nodes are enlarged in most mice by 4-6 months of age
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• severe splenic lymphoid hyperplasia at 6 months of age
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• mice exhibit multi-organ inflammation, lymphoid hyperplasia, vasculitis, and kidney disease; lupus-like inflammatory disease is associated with immune activation, production of autoantibodies to dsDNA, and deposition of
immune complexes in the kidney
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• significantly increased serum-total anti-dsDNA antibody levels
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• inflammation of varying severity is observed in the heart, lung, salivary gland, pancreas, and occasionally other organs including the lacrimal gland, at 6 months of age
• inflammatory infiltrates consist of lymphocytes and large numbers of antibody-producing plasma cells
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• inflammatory cells primarily surrounding salivary gland ducts
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• occasionally
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• widespread to diffuse, global to segmental membranoproliferative glomerulonephritis
• immunofluorescence of frozen kidney sections showed glomerular immunocomplexes containing IgG
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• lymphoplasmacytic tubulointerstitial nephritis
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• inflammatory cells primarily surrounding bronchioles
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hematopoietic system
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• enlarged spleens as early as 4 months of age
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• significantly increased spleen weight at 4 and 6 months of age
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• increased B220+ B cell numbers in spleen
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• increased CD138+ plasma cell numbers in spleen
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• increased number of CD4+ T cells in spleen
• however, the number of splenic CD8+ T cells is normal
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• increased regulatory T cell number in spleen
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• increased splenic nucleated cell count
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• significantly increased total serum IgG levels
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• both CD4+ and CD8+ splenocytes show up-regulated expression of the activation marker CD69
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renal/urinary system
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• lymphoplasmacytic tubulointerstitial nephritis
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• severe kidney disease at 6 months of age
• chronic kidney disease as evidenced by shrunken and pitted kidney morphology in one euthanized mouse
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• widespread to diffuse, global to segmental membranoproliferative glomerulonephritis
• immunofluorescence of frozen kidney sections showed glomerular immunocomplexes containing IgG
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homeostasis/metabolism
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• 87.5% of euthanized mice show atrial thromboses
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liver/biliary system
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• 87.5% of euthanized mice show chronic passive congestion of the liver
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respiratory system
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• inflammatory cells primarily surrounding bronchioles
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atelectasis
(
J:220965
)
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• 87.5% of euthanized mice show pulmonary atelectasis
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endocrine/exocrine glands
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• inflammatory cells primarily surrounding salivary gland ducts
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• occasionally
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digestive/alimentary system
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• inflammatory cells primarily surrounding salivary gland ducts
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vision/eye
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• occasionally
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reproductive system
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• mice mate successfully up to at least 6 months of age but have slightly smaller average litters than wild-type controls (4.6 versus 5.8, respectively)
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growth/size/body
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• hearts of clinically healthy mice are often mildly to markedly enlarged
• 87.5% of euthanized mice show markedly enlarged hearts
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• enlarged spleens as early as 4 months of age
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• significantly increased spleen weight at 4 and 6 months of age
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