Analysis Tools
mortality/aging
| N |
• homozygotes are obtained at the expected Mendelian ratios and appear healthy with no evidence of viral or bacterial infections
(J:50436)
• mice do not differ from wild-type control in their postnatal lethality rates associated with corn dust bedding
(J:130297)
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hematopoietic system
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• at 3 and 5 days after infection with influenza A virus, homozygotes exhibit a significantly increased % of neutrophils in BAL fluid relative to wild-type mice
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• enlarged, foamy macrophages containing SP-B positive material are frequently found in alveoli adjacent to bronchiolar-associated monocytic infiltrates
(J:50436)
• at >3 weeks, homozygotes display enlarged airspaces and infiltration with atypical, foamy, alveolar macrophages
(J:62282)
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• homozygotes exhibit a 4-fold increase in macrophage number in alveolar lavage
(J:50436)
• at 2 weeks, homozygotes exhibit increased numbers of normal-appearing alveolar macrophages relative to wild-type mice
(J:62282)
• at >3 weeks, homozygotes exhibit multiple foci of hypertrophic, foamy, alveolar macrophages throughout the lungs, with focal areas of macrophage accumulation and perivascular/peribronchiolar monocytic infiltrates noted by 7 months
(J:62282)
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• ~22% of alveolar macrophages are abnormally large with a diameter of twice normal
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• at 3 days after infection with influenza A virus, homozygotes exhibit significantly reduced myeloperoxidase activity in isolated BAL neutrophils relative to wild-type mice
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• mutant alveolar macrophages exhibit a 10-fold increase in hydrogen peroxide production, as well as increased activity of matrix metalloproteinases MMP2 and MMP9, and increased immunostaining for MMP9 and MMP12
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homeostasis/metabolism
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• homozygotes exhibit pulmonary lipoidosis without accumulation of surfactant proteins B or C, or their mRNAs, as well as a 3-fold increase in alveolar, tissue and total saturated phospatidylcholine pool sizes
• isolated lipid aggregates appear enlarged and organized into electron dense phospholipid arrays with reduced tubular myelin
• absence of changes in surfactant proteins distinguishes pulmonary lipoidosis from other alveolar proteinosis models
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• at 3 and 9 weeks, homozygotes exhibit an ~2-fold increase in basal levels of IL-1beta in lung homogenates; however, IL-1beta does not reach levels typically detected in severe inflammation
(J:62282)
• no significant changes in TNF, macrophage inflammatory protein 2 or IL-6 are observed
(J:62282)
• at 3 and 5 days after infection with influenza A virus, homozygotes exhibit significantly increased IL-1beta concentrations in lung homozgenates relative to wild-type mice
(J:72681)
• at 5 days after infection with influenza A virus, homozygotes exhibit a ~25% increase in IFN-gamma concentrations in lung homozgenates relative to wild-type mice
(J:72681)
• at 3 and 5 days after infection with influenza A virus, homozygotes exhibit significantly increased IL-6 concentrations in lung homozgenates relative to wild-type mice
(J:72681)
• intratracheal co-administration of recombinant SP-D significantly reduces IL-6 levels in the mutant lung
(J:72681)
• at 3 and 5 days after infection with influenza A virus, homozygotes exhibit significantly increased TNF concentrations in lung homozgenates relative to wild-type mice
(J:72681)
• intratracheal co-administration of recombinant SP-D significantly reduces TNF levels in the mutant lung
(J:72681)
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• at 3 and 5 days after infection with influenza A virus, homozygotes exhibit significantly increased MIP-2 concentrations in lung homozgenates relative to wild-type mice
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immune system
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• at 3 and 5 days after infection with influenza A virus, homozygotes exhibit a significantly increased % of neutrophils in BAL fluid relative to wild-type mice
|
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• enlarged, foamy macrophages containing SP-B positive material are frequently found in alveoli adjacent to bronchiolar-associated monocytic infiltrates
(J:50436)
• at >3 weeks, homozygotes display enlarged airspaces and infiltration with atypical, foamy, alveolar macrophages
(J:62282)
|
|
• homozygotes exhibit a 4-fold increase in macrophage number in alveolar lavage
(J:50436)
• at 2 weeks, homozygotes exhibit increased numbers of normal-appearing alveolar macrophages relative to wild-type mice
(J:62282)
• at >3 weeks, homozygotes exhibit multiple foci of hypertrophic, foamy, alveolar macrophages throughout the lungs, with focal areas of macrophage accumulation and perivascular/peribronchiolar monocytic infiltrates noted by 7 months
(J:62282)
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• ~22% of alveolar macrophages are abnormally large with a diameter of twice normal
|
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• at 3 days after infection with influenza A virus, homozygotes exhibit significantly reduced myeloperoxidase activity in isolated BAL neutrophils relative to wild-type mice
|
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• mutant alveolar macrophages exhibit a 10-fold increase in hydrogen peroxide production, as well as increased activity of matrix metalloproteinases MMP2 and MMP9, and increased immunostaining for MMP9 and MMP12
|
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• at 3 and 9 weeks, homozygotes exhibit an ~2-fold increase in basal levels of IL-1beta in lung homogenates; however, IL-1beta does not reach levels typically detected in severe inflammation
(J:62282)
• no significant changes in TNF, macrophage inflammatory protein 2 or IL-6 are observed
(J:62282)
• at 3 and 5 days after infection with influenza A virus, homozygotes exhibit significantly increased IL-1beta concentrations in lung homozgenates relative to wild-type mice
(J:72681)
• at 5 days after infection with influenza A virus, homozygotes exhibit a ~25% increase in IFN-gamma concentrations in lung homozgenates relative to wild-type mice
(J:72681)
• at 3 and 5 days after infection with influenza A virus, homozygotes exhibit significantly increased IL-6 concentrations in lung homozgenates relative to wild-type mice
(J:72681)
• intratracheal co-administration of recombinant SP-D significantly reduces IL-6 levels in the mutant lung
(J:72681)
• at 3 and 5 days after infection with influenza A virus, homozygotes exhibit significantly increased TNF concentrations in lung homozgenates relative to wild-type mice
(J:72681)
• intratracheal co-administration of recombinant SP-D significantly reduces TNF levels in the mutant lung
(J:72681)
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• at 3 and 5 days after infection with influenza A virus, homozygotes exhibit significantly increased MIP-2 concentrations in lung homozgenates relative to wild-type mice
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• homozygotes develop chronic lung inflammation associated with hypertrophic alveolar macrophages and peribronchiolar-perivascular monocytic infiltrates
(J:62282)
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• homozygotes exhibit reduced pulmonary clearance of intranasally administered Phil/82 strain of influenza A virus (IAV); intratracheal co-administration of recombinant SP-D enhances clearance of Phil/82 virus
• in contrast, homozygotes exhibit efficient pulmonary clearance of a less glycosylated strain of IAV (Mem71), which is relatively resistant to the effects of SP-D in vitro
• notably, homozygotes display no differences in alveolar macrophage phagocytosis of IAV relative to wild-type mice
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respiratory system
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• homozygotes develop chronic lung inflammation associated with hypertrophic alveolar macrophages and peribronchiolar-perivascular monocytic infiltrates
(J:62282)
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• homozygotes display heterogeneous abnormalities in lung parenchyma, with focal areas of alveolar macrophage accumulation noted throughout the lungs
(J:50436)
• starting at 3 weeks, mutant lungs exhibit progressive enlargement of alveolar macrophages, with multiple foci of large, foamy, alveolar macrophages observed by 6 weeks
(J:62282)
• by 6-7 months, individual homozygotes exhibit a moderate to severe airspace enlargement, with focal areas of macrophage accumulation and perivascular/peribronchiolar monocytic infiltrates
(J:62282)
• at 7 months, the parenchyma of mutant lungs shows increased elastin deposition, with short, thick, and more highly coiled elastic fibers than wild-type lungs
(J:62282)
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• ~22% of alveolar macrophages are abnormally large with a diameter of twice normal
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• homozygotes exhibit accumulation of surfactant lipids in the alveolar space
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• homozygotes display thickened alveolar septa adjacent to focal sites of macrophage accumulation
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• homozygotes display progressive pulmonary emphysema, with moderate to severe emphysematous changes noted by 7 months of age
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• by 7 months, mutant alveolar septa show increased elastin staining, with elastic fibers appearing shorter, thicker, and more highly coiled than wild-type fibers
• however, elastin staining is reduced in alveolar septa adjacent to foci of macrophage accumulation and fibrosis
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• homozygotes develop mild subpleural fibrotic lesions associated with increased collagen deposition in focal areas of alveolar macrophage accumulation and in alveolar septa
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• at 3 and 6 weeks, homozygotes display increased lung volume-to-body weight ratios relative to wild-type mice; however, no changes in wet lung weight, total lung DNA, or protein content are noted at 5 months
• by 3 weeks, homozygotes show a significant increase in the % fractional area devoted to airspace; at this time, the % fractional area of respiratory parenchyma is reduced
• at 12 weeks, homozygotes exhibit significantly increased lung volumes, consistent with emphysematous changes
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• altered surfactant phospholipid structures are observed
• total saturated phosphatidylcholine levels are increased in alveolar lavage and lung homogenates
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• total surfactant in alveolar lavage fluid is elevated
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growth/size/body
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• homozygotes exhibit a slight reduction in body weight prior to weaning; however, no significant differences are observed after 3 weeks of age
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weight loss
(
J:72681
)
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• following intranasal infection with influenza A virus, homozygotes exhibit a greater % of weight loss than wild-type mice during the 4 days post-infection
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