Mouse Genome Informatics
hm1
    Ptger4tm1Aic/Ptger4tm1Aic
involves: 129P2/OlaHsd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• less than 5% of homozygotes survive and grow normally for more than 1 year
• greater than 95% of F2 homozygotes die within 72 hours after birth

cardiovascular system
N
• F2 homozygotes obtained by selective bleeding exhibit normal basal heart rate levels relative to wild-type mice (J:92865)
• 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 (J:92865)
• no significant changes in heart rate levels or plasma creatinine levels are noted at day 14 of 2K1C (J:92865)
• moribund homozygotes display dilated pulmonary arteries
• homozygotes display significant congestion of pulmonary capillaries
• 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
• moribund homozygotes exhibit left-sided heart failure

respiratory system
• homozygotes display significant congestion of pulmonary capillaries
• moribund homozygotes exhibit disorganized and shrunken alveoli

behavior/neurological
• homozygotes become lethargic with significantly weakened movements at ~24 hours after birth

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)

skeleton
• 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)
• 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

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)
• 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)
• DNFB-sensitized homozygotes display reduced antigen-specific T-cell proliferation in the regional lymph nodes
• 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
• 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
• 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
• lymphocytes isolated from regional lymph nodes of DNBS-sensitized homozygotes show a significant reduction in IFN-gamma production

hematopoietic system
• 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)
• DNFB-sensitized homozygotes display reduced antigen-specific T-cell proliferation in the regional lymph nodes
• 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

integument
• homozygotes become pale at ~24 hours after birth

cellular
• 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)

Mouse Models of Human Disease
OMIM IDRef(s)
Patent Ductus Arteriosus 607411 J:47618


Mouse Genome Informatics
hm2
    Ptger4tm1Aic/Ptger4tm1Aic
involves: 129P2/OlaHsd * C57BL/6Cr
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• male suvivors of the F2 progeny treated with colon carcinogen azoxymethane exhibit significantly reduced numbers of aberrant crypt foci per colon (56% of wild-type values)
• all male homozygotes treated with colon carcinogen azoxymethane develop aberrant crypt foci, i.e. putative preneoplastic lesions in the colon, albeit with reduced numbers of foci per colon
• preneoplastic lesions are not associated with significant changes in body or organ weights

homeostasis/metabolism
• male suvivors of the F2 progeny treated with colon carcinogen azoxymethane exhibit significantly reduced numbers of aberrant crypt foci per colon (56% of wild-type values)