Analysis Tools
mortality/aging
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• over 20% are moribund by around 10 - 12 months of age
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• about 40% - 50% of pups die within 1 - 4 days of birth
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homeostasis/metabolism
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• seen in ecchymotic areas of the uterus in retired breeders
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• at 10 month of age, 3 of 52 have mural thrombi of the atrium with marked fibrosis of the adjacent myocardium
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• injection of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at 40 ug/kg fails to increase expression of Cyp1a1, Cyp1a2, or Ugt1a6a
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reproductive system
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• in 12 retired breeders ecchymotic areas are seen on the serosa and are identified histologically by hypertrophy, thromboses, and mineralization of the serosal vessels
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• after 3 - 4 cycles females have trouble maintaining pregnancies
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• coincident with development of uterine lesions
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immune system
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• in about 80% of mice reduced T- and B-cell area is accompanied by mild to moderate splenomegaly
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• myeloid hyperplasia of the red pulp is seen in mice with mild to moderate splenomegaly
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small spleen
(
J:25048
)
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• at 4 weeks of age; however, spleen architecture is similar to wild-type
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• at 2 - 3 weeks of age, spleens contain 75 - 85% fewer lymphocytes; however the number of lymphocytes is similar to wild-type by 10 - 12 weeks of age
• at 25 - 32 weeks of age, lymphocyte numbers are about 50% of wild-type
• however, the proportion of B and T cells is similar to wild-type and thymus cellularity is similar to wild-type
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• significant decrease in the size of the T- and B-cell zones and in the number of T- and B-cells in the spleen
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• in pups that die postnatally lymphocyte infiltration is seen in many organs, particularly in the gut, urinary tract, and lung
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• at 10 month of age, 25% of hearts display chronic, focal inflammation in the myocardium of the ventricles or atrium
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• in some cases of rectal prolapse colonic hyperplasia and severe inflammation are also seen
• in mice with prolapse many helical bacteria are present in the crypts and significant titers of antibodies against Helicobacter hepaticus are detected
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• mild to moderate inflammation is seen in some homozygotes
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folliculitis
(
J:44690
)
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• ruptured follicles are associated with a mixed inflammatory cell infiltrate
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liver/biliary system
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• mild to moderate inflammation is seen in some homozygotes
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• centrilobular hypercellularity
(J:25048)
• hepatic portal vascular lesions characterized by increased numbers of arteries and arterioles
(J:44690)
• however, Heliobacter hepaticus hepatitis is not seen
(J:44690)
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• eosinophilia is seen in periportal hepatocytes
(J:25048)
• hepatocytomegalic periportal hepatocytes with eosinophilic cytoplasm
(J:44690)
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• a 4 weeks of age, liver weight is 2.9 +/- 0.3% of body weight compared to 6.1 +/- 0.4% in wild-type mice
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• seen in 1 of 12 mice at 11-13 months of age
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• seen in 3 of 12 mice at 11-13 months of age
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• pronounced fibrosis of the portal tract, visible at 3 weeks of age
(J:25048)
• minimal to mild portal fibrosis
(J:44690)
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• constitutive expression of Cyp1a2 and Ugt1a6a are decreased by 90 +/- 5% and 85 +/- 5%, respectively, relative to wild-type mice
• liver glycogen depletion
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growth/size/body
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• seen around 9 months of age
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• at 10 months of age, heart weight is increased to 0.8 +/- 0.13% of body weight compared to 0.47 +/- 0.06% in wild-type mice
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weight loss
(
J:44690
)
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• a 15 - 20% weight loss is seen in over 20% of mice by around 10 - 12 months of age
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• slower growth rate within the first 2 - 4 weeks of life
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• in about 80% of mice reduced T- and B-cell area is accompanied by mild to moderate splenomegaly
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digestive/alimentary system
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• seen in several homozygotes
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• in some cases of rectal prolapse colonic hyperplasia and severe inflammation are also seen
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• at 6 - 13 months of age, 48% develop rectal prolapse
• in mice over 9 months of age, prolapse is characterized by marked epithelial hyperplasia and mucus secretion in the submucosa
• in mice with prolapse many helical bacteria are present in the crypts and significant titers of antibodies against Helicobacter hepaticus are detected; however prolapse has been seen in mice from 4 different animal facilities and mice with and without prolapse are seen in the same cage when housed in groups
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• pyloric regions of the glandular stomach display focal, proliferative lesions with the highest incidence in mice over 9 months of age
• lesions start as focal hyperplasia and progress to large plaques or polyps
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• lesions in the pyloric region of the glandular stomach start as focal hyperplasia and progress to large plaques or polyps
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• in some cases of rectal prolapse colonic hyperplasia and severe inflammation are also seen
• in mice with prolapse many helical bacteria are present in the crypts and significant titers of antibodies against Helicobacter hepaticus are detected
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cardiovascular system
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• mineralization of the serosal vessels in ecchymotic areas of the uterus
• hepatic portal vascular lesions characterized by increased numbers of arteries and arterioles
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• at 10 month of age, almost 10% have enlarged coronary arteries and arterioles due to smooth muscle hypertrophy
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• at 10 month of age, almost 10% have enlarged coronary arteries and arterioles due to smooth muscle hypertrophy
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• seen around 9 months of age
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• at 10 months of age, heart weight is increased to 0.8 +/- 0.13% of body weight compared to 0.47 +/- 0.06% in wild-type mice
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• at 10 month of age, 25% of hearts display fibrosis in the myocardium of the ventricles or atrium
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• at 10 month of age, 25% of hearts display chronic, focal inflammation in the myocardium of the ventricles or atrium
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neoplasm
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• seen in 1 of 12 mice at 11-13 months of age
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• seen in 3 of 12 mice at 11-13 months of age
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hematopoietic system
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• in about 80% of mice reduced T- and B-cell area is accompanied by mild to moderate splenomegaly
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• myeloid hyperplasia of the red pulp is seen in mice with mild to moderate splenomegaly
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small spleen
(
J:25048
)
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• at 4 weeks of age; however, spleen architecture is similar to wild-type
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• at 2 - 3 weeks of age, spleens contain 75 - 85% fewer lymphocytes; however the number of lymphocytes is similar to wild-type by 10 - 12 weeks of age
• at 25 - 32 weeks of age, lymphocyte numbers are about 50% of wild-type
• however, the proportion of B and T cells is similar to wild-type and thymus cellularity is similar to wild-type
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• significant decrease in the size of the T- and B-cell zones and in the number of T- and B-cells in the spleen
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muscle
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• at 10 month of age, almost 10% have enlarged coronary arteries and arterioles due to smooth muscle hypertrophy
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integument
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• make up 25 - 50% of plucked truncal pelage hairs rather than 10% as in wild-type mice
• hair fibers have worn rounded edges, worn cuticular scales, and some areas with small surface blebs with folding and breaking at the fold sites
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• dystrophic follicles may have an abnormal hair fiber
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• follicles are widely separated and dystrophic
• dystrophic follicles are empty, markedly dilated at the piliary canal and have either a structurally abnormal hair fiber or are ruptured
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folliculitis
(
J:44690
)
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• ruptured follicles are associated with a mixed inflammatory cell infiltrate
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• dilation of the piliary canal
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• hypergranulosis is associated with the healing of skin ulcers
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acanthosis
(
J:44690
)
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• mild to moderate acanthosis is associated with the healing of skin ulcers
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scaly skin
(
J:44690
)
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• at 6 - 13 months of age, 53% develop dorsal, localized, thick, scaly skin
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skin lesions
(
J:44690
)
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• progressive focal lesions are seen on the dorsal skin and in some mice extend to the ears and lateral aspects of the abdomen
• dermal mastocytosis is common in areas of inflamed skin
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• skin lesions progress from alopecia to ulcers of variable severity
• ulcers heal by lateral hyperplasia of the intact epithelium with dermal scarring
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thick skin
(
J:44690
)
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• at 6 - 13 months of age, 53% develop dorsal, localized, thick, scaly skin
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