Analysis Tools
mortality/aging
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• less than 5% of homozygotes survive and grow normally for more than 1 year
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• greater than 95% of F2 homozygotes die within 72 hours after birth
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cardiovascular system
| N |
• F2 homozygotes obtained by selective bleeding exhibit normal basal heart rate levels relative to wild-type mice
• in a two-kidney, one-clip hypertension model (2K1C), F2 homozygotes obtained by selective bleeding show no significant differences in the degree and time-course of renovascular hypertension relative to F2 wild-type mice
• no significant changes in heart rate levels or plasma creatinine levels are noted at day 14 of 2K1C
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• moribund homozygotes display dilated pulmonary arteries
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• homozygotes display significant congestion of pulmonary capillaries
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• the DA remains fully open with a thin wall in 6-hr-old homozygotes that still appear healthy, but fails to close completely in moribund neonates
• surviving homozygotes exhibit a DA that is either partially closed or severely narrowed
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• moribund homozygotes exhibit left-sided heart failure
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respiratory system
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• homozygotes display significant congestion of pulmonary capillaries
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• moribund homozygotes exhibit disorganized and shrunken alveoli
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behavior/neurological
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• homozygotes become lethargic with significantly weakened movements at ~24 hours after birth
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homeostasis/metabolism
| N |
• homozygotes exhibit a normal febrile response to PGE2
(J:70534)
• on a low-salt diet, F2 homozygotes obtained by selective bleeding display an increase in plasma renin activity that is comparable to that in F2 wild-type mice
(J:92865)
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skeleton
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• in culture, TRAP-positive osteoclasts are formed in dibutyryl cAMP-treated calvaria, but not in PGE2-treated calvaria
• PGE2-induced osteoclast formation is also diminished in bone marrow cultures (not shown)
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• in culture, calvaria and long bones isolated from mutant neonates show a significant reduction in PGE2-induced bone resorption
• in contrast, dibutyryl cAMP-stimulated bone resorption occurs similarly in wild-type and mutant calvaria and long bones
• notably, PGE2-induction of MMP-2 and MMP-13 is markedly impaired in calvarial cultures from mutant neonates
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immune system
| N |
• ovalbumin-sensitized homozygotes display a normal delayed-type hypersensitivity response, as measured by footpad swelling after ovalbumin challenge
(J:83725)
• in addition, homozygotes exhibit a normal acute inflammatory response to 12-O-tetradecanoylphorbol-13-acetate
(J:83725)
• in a model of IgE antigen-dependent passive cutaneous anaphylaxis, mice exhibit normal dye extravasation (a measure of edema)
(J:197334)
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• in culture, TRAP-positive osteoclasts are formed in dibutyryl cAMP-treated calvaria, but not in PGE2-treated calvaria
• PGE2-induced osteoclast formation is also diminished in bone marrow cultures (not shown)
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• DNFB-sensitized homozygotes display reduced antigen-specific T-cell proliferation in the regional lymph nodes
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• in culture, calvaria and long bones isolated from mutant neonates show a significant reduction in PGE2-induced bone resorption
• in contrast, dibutyryl cAMP-stimulated bone resorption occurs similarly in wild-type and mutant calvaria and long bones
• notably, PGE2-induction of MMP-2 and MMP-13 is markedly impaired in calvarial cultures from mutant neonates
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• at 24 hrs after FITC exposure, female homozygotes of the F2 progeny show a significantly reduced accumulation of Langerhans cells in their regional lymph nodes
• in vitro, mutant skin explants exhibit reduced Langerhans cell emigration into the medium relative to wild-type explants; emigration is not affected by an EP4 agonist or antagonist
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• homozygotes exhibit reduced ear swelling, spongiosis and infiltration of lymphocytes in the edematous dermis in the contact hypersensitivity reaction, using dinitrofluorobenzene as the sensitizing agent
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• lymphocytes isolated from regional lymph nodes of DNBS-sensitized homozygotes show a significant reduction in IFN-gamma production
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hematopoietic system
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• in culture, TRAP-positive osteoclasts are formed in dibutyryl cAMP-treated calvaria, but not in PGE2-treated calvaria
• PGE2-induced osteoclast formation is also diminished in bone marrow cultures (not shown)
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• DNFB-sensitized homozygotes display reduced antigen-specific T-cell proliferation in the regional lymph nodes
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• in culture, calvaria and long bones isolated from mutant neonates show a significant reduction in PGE2-induced bone resorption
• in contrast, dibutyryl cAMP-stimulated bone resorption occurs similarly in wild-type and mutant calvaria and long bones
• notably, PGE2-induction of MMP-2 and MMP-13 is markedly impaired in calvarial cultures from mutant neonates
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integument
cellular
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• the DA remains fully open with a thin wall in 6-hr-old homozygotes that still appear healthy, but fails to close completely in moribund neonates
• surviving homozygotes exhibit a DA that is either partially closed or severely narrowed
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• in culture, TRAP-positive osteoclasts are formed in dibutyryl cAMP-treated calvaria, but not in PGE2-treated calvaria
• PGE2-induced osteoclast formation is also diminished in bone marrow cultures (not shown)
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• DNFB-sensitized homozygotes display reduced antigen-specific T-cell proliferation in the regional lymph nodes
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