Analysis Tools
mortality/aging
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• about a third die before weaning
• dead mice are about half the weight of surviving littermate
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endocrine/exocrine glands
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• vacuolization occurs as a result of premature activation of digestive enzymes
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• zymogen granules (ZGs) are observed at much higher (almost 2-fold) abundance compared to wild-type acini
• after Cch (carbachol) stimulation, number of zymogen granules remaining in acini is relatively greater than in wild-type
• in ED/Cch-treated mice (chronic ethanol exposure through diet, ED, with carbachol treatment, Cch), zymogen granule content in acini is increased compared to treated controls
• in wild-type acini, ZGs are concentrated at apical poles compared to a wider distribution beyond apical regions in mutant acini
• in ED/Cch-treated wild-type tissue, 16% of ZGs are docked onto lateral plasma membrane compared to only 1% in treated mutants; very few ZG-ZG fusions are observed in treated mutants relative to controls
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• zymogen granules accumulate in the acinar cells of the pancreas
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• regulated amylase secretion by acini in adults is substantially reduced relative to wild-type upon submaximal and maximal carbachol (Cch) stimulation
• in ED/Cch-treated mice, amylase secretion by acini is significantly reduced compared to matched wild-type controls
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• alcoholic pancreatitis induced by chronic alcohol exposure through diet (ED) followed by injection of carbachol (Cch) is reduced in severity in mutants compared to wild-type mice
• parenchymal edema, necrosis with leukocyte infiltration, fat necrosis, congested blood vessels within peripancreatic fat, and hemorrhage were observed in treated mutants with greatly reduced severity than in controls
• lung pathology (inflammation, edema, leukocyte infiltration, capillary congestion and hemorrhage) is much milder in ED/Cch-treated mutants than in controls
• similar results are observed in a supramaximal cerulein-induced pancreatitis model
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immune system
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• mast cell development is unaffected with differences in morphology or numbers relative to wild-type, or in morphology or numbers of intracellular granules
• mast cells are not impaired in cytokine/chemokine production
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• release of beta-hexosaminidase and histamine is markedly inhibited; kinetics of histamine release are decreased compared to wild-type
• early signaling events are unaffected in mutants, but when these events are by-passed by PMA or thapsigargin treatment, release of beta-hexosaminidase from cytoplasmic granules is inhibited
• wild-type mast cells do have a slightly but significantly higher proportion of immature granules with no electron-dense material although intragranular histamine content is similar
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• born marrow-derived dendritic cells show increased activity (48% greater) compared to wild-type cells
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• mutants primed by injection of anti-DNP IgE Ab followed in 24 hours by DNP challenge show reduced blood levels of histamine 60 minutes after challenge
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digestive/alimentary system
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• vacuolization occurs as a result of premature activation of digestive enzymes
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• zymogen granules (ZGs) are observed at much higher (almost 2-fold) abundance compared to wild-type acini
• after Cch (carbachol) stimulation, number of zymogen granules remaining in acini is relatively greater than in wild-type
• in ED/Cch-treated mice (chronic ethanol exposure through diet, ED, with carbachol treatment, Cch), zymogen granule content in acini is increased compared to treated controls
• in wild-type acini, ZGs are concentrated at apical poles compared to a wider distribution beyond apical regions in mutant acini
• in ED/Cch-treated wild-type tissue, 16% of ZGs are docked onto lateral plasma membrane compared to only 1% in treated mutants; very few ZG-ZG fusions are observed in treated mutants relative to controls
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• zymogen granules accumulate in the acinar cells of the pancreas
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homeostasis/metabolism
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• in contrast to ED/Cch-treated controls in which amylase levels are increased 10-fold, mutants exhibit a 5.7-fold elevation in serum amylase
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• treated controls show 250-fold increase in serum lipase levels compared to a 78-fold increase in mutants
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• myeloperoxidase activity is reduced in ED/Cch-treated mutants than in controls
• in ED/Cch-treated and control diet-fed mutants, amylase activity is 2-fold higher than wild-type
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growth/size/body
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• surviving mice are 80-90% normal size by the time of sexual maturity
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hematopoietic system
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• release of beta-hexosaminidase and histamine is markedly inhibited; kinetics of histamine release are decreased compared to wild-type
• early signaling events are unaffected in mutants, but when these events are by-passed by PMA or thapsigargin treatment, release of beta-hexosaminidase from cytoplasmic granules is inhibited
• wild-type mast cells do have a slightly but significantly higher proportion of immature granules with no electron-dense material although intragranular histamine content is similar
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cellular
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• release of beta-hexosaminidase and histamine is markedly inhibited; kinetics of histamine release are decreased compared to wild-type
• early signaling events are unaffected in mutants, but when these events are by-passed by PMA or thapsigargin treatment, release of beta-hexosaminidase from cytoplasmic granules is inhibited
• wild-type mast cells do have a slightly but significantly higher proportion of immature granules with no electron-dense material although intragranular histamine content is similar
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