Analysis Tools
respiratory system
enlarged lung
(
J:78819
)
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• by 6-8 months of age, mutant lungs exceeded normal size by 3-fold
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• by 6-8 months, alveolar spaces are significantly reduced in number
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atelectasis
(
J:78819
)
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• at 24-32 wks of age, the lobular connective tissue is reduced and replaced by multifocal atelectatic areas
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• by 6-8 months, alveolar spaces are enlarged and inflated
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• by 6-8 months, alveoli are surrounded by thin, dysplastic, and frequently incomplete septal walls
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• a mild emphysema-like condition is already evident at birth and progresses with increasing age
• a moderate emphysema associated with rupture of septal walls is observed at 12-14 wks
• severe emphysema with extensive atelectatic areas is noted by 24-32 wks
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• at 12 wks of age, mutant lungs lack normal elastic fibers and display multiple patches of fragmented and condensed elastin, unlike wild-type lungs
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• by 6-8 months, most mice develop severe dyspnea and need to be sacrificed
• mice remain clinically healthy up to 6 months of age but their health deteriorates therefater
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• an almost complete loss of pulmonary elasticity is observed at 24-32 wks of age
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digestive/alimentary system
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• extensive edema in the mucosal layer of the colorectal region at 4 wks of age
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• at 12-14 weeks of age, intestinal goblet cell numbers are increased
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• colorectal adenocarcinomas are formed by enlarged and dysplastic crypts lined by neoplastic epithelial cells
• crypts display various degrees of epithelial cell detachment and infiltrate all layers of the colorectal wall
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• superficial rectal ulcerations noted at 4 months of age
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• by 4 wks of age, solitary ulcers associated with epithelial hyperplasia and occasional crypts infiltrating the submucosal layer of the colonic wall are observed
• at 12 wks of age, mutant colons lack normal elastic fibers and display multiple patches of fragmented and condensed elastin, unlike wild-type colons
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• by 4 wks of age, mice develop a rectal prolapse induced by extensive edema in the mucosal layer of the colorectal region
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• at 12-14 wks of age, most animals develop adenomas consisting of enlarged and abnormally branched cystic glands with increased numbers of goblet cells
• by 6-8 months, all mice show invasive colorectal carcinomas in the distal portion of the colorectum with diameters of 0.7-1.5 cm
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• at autopsy, massive inflammatory infiltrations of the colonic wall associated with a reactive splenomegaly are observed
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• by 6-8 months, most mice exhibit rectal prolapse infections that frequently progress to ulcerative proctitis
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cardiovascular system
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• ubiquitous myofibrillar hypertrophy is observed at 24-32 wks of age
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• by 6-8 months, the cardiac/body weight index exceeds normal values by 30%
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• cardiomyopathy progresses from initial right ventricular dilatation (12-14 wks) to biventricular dilatation (24-32 wks)
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• at 12-14 wks of age, a moderate cardiomyopathy associated with right ventricular dilatation is observed; not seen at 4-6 wks of age
• by 24-32 wks of age, biventricular dilatation is observed
• however, elastic fibers in the heart appear normal, suggesting that the cardiomyopathy is mostly secondary to emphysema
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neoplasm
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• at 12-14 wks of age, most animals develop adenomas consisting of enlarged and abnormally branched cystic glands with increased numbers of goblet cells
• by 6-8 months, all mice show invasive colorectal carcinomas in the distal portion of the colorectum with diameters of 0.7-1.5 cm
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immune system
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• at autopsy, massive inflammatory infiltrations of the colonic wall associated with a reactive splenomegaly are observed
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• by 6-8 months, most mice exhibit rectal prolapse infections that frequently progress to ulcerative proctitis
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• reactive splenomegaly is observed upon autopsy at 6-8 months of age
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muscle
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• ubiquitous myofibrillar hypertrophy is observed at 24-32 wks of age
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• at 12-14 wks of age, a moderate cardiomyopathy associated with right ventricular dilatation is observed; not seen at 4-6 wks of age
• by 24-32 wks of age, biventricular dilatation is observed
• however, elastic fibers in the heart appear normal, suggesting that the cardiomyopathy is mostly secondary to emphysema
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endocrine/exocrine glands
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• colorectal adenocarcinomas are formed by enlarged and dysplastic crypts lined by neoplastic epithelial cells
• crypts display various degrees of epithelial cell detachment and infiltrate all layers of the colorectal wall
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hematopoietic system
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• reactive splenomegaly is observed upon autopsy at 6-8 months of age
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cellular
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• at 12-14 weeks of age, intestinal goblet cell numbers are increased
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• impaired export and/or deposition of small latent Tgfb1 in the extracellular matrix, resulting in the absence of extracellular Tgfb1 in affected tissues (lung, colon, and heart) but not in kidney
• as a result, epithelial cells show reduced levels of phosphorylated Smad2 proteins, overexpress Myc, and undergo uncontrolled proliferation
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growth/size/body
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• by 6-8 months, the cardiac/body weight index exceeds normal values by 30%
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enlarged lung
(
J:78819
)
|
• by 6-8 months of age, mutant lungs exceeded normal size by 3-fold
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• reactive splenomegaly is observed upon autopsy at 6-8 months of age
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