Mouse Genome Informatics
hm1
    Ptger2tm1Brey/Ptger2tm1Brey
B6.129S6-Ptger2tm1Brey
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• after middle cerebral artery occlusion induced infarction cerebral blood flow in the non-ischemic contralateral hemisphere is increased compared to wild-type controls
• following 90 min of ischemia induced by middle cerebral artery occlusion and 22.5 h of reperfusion infarct size is significantly larger in mutant males compared to wild-type male controls
• however, no differences in cerebral blood flow in the ischemic hemisphere before, during or after occlusion are detected

nervous system
• following 90 min of ischemia induced by middle cerebral artery occlusion and 22.5 h of reperfusion infarct size is significantly larger in mutant males compared to wild-type male controls
• however, no differences in cerebral blood flow in the ischemic hemisphere before, during or after occlusion are detected

behavior/neurological
• in a Morris water maze mice show longer escape latencies on each day of testing


Mouse Genome Informatics
hm2
    Ptger2tm1Brey/Ptger2tm1Brey
C.129S6-Ptger2tm1Brey
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• display enhanced phagocytosis of Abeta plaques in an in vitro assay using hippocampal sections from Alzheimer's disease patients
• microglia show enhanced activation and tend to aggregate around Abeta plaques when incubated with hippocampal sections from Alzheimer disease patients
• in culture primary microglial cells show some signs of an activated phenotype but do not display an increase in proliferation
• cultures of mutant microglial cells and wild-type neurons exposed to ABeta1-42 show no signs of the neurotoxicity seen when wild-type microglial cells are used
• PGE2 and a PTGER2 agonist fail to induce changes in synaptic activity
• in hippocampal slices at 40 and 120 min after theta burst stimulation
• LPS fails to elevate LTP at hippocampal perforant path dentate granule cell synapses

immune system
• display enhanced phagocytosis of Abeta plaques in an in vitro assay using hippocampal sections from Alzheimer's disease patients
• microglia show enhanced activation and tend to aggregate around Abeta plaques when incubated with hippocampal sections from Alzheimer disease patients
• in culture primary microglial cells show some signs of an activated phenotype but do not display an increase in proliferation
• cultures of mutant microglial cells and wild-type neurons exposed to ABeta1-42 show no signs of the neurotoxicity seen when wild-type microglial cells are used

hematopoietic system
• display enhanced phagocytosis of Abeta plaques in an in vitro assay using hippocampal sections from Alzheimer's disease patients
• microglia show enhanced activation and tend to aggregate around Abeta plaques when incubated with hippocampal sections from Alzheimer disease patients
• in culture primary microglial cells show some signs of an activated phenotype but do not display an increase in proliferation
• cultures of mutant microglial cells and wild-type neurons exposed to ABeta1-42 show no signs of the neurotoxicity seen when wild-type microglial cells are used


Mouse Genome Informatics
hm3
    Ptger2tm1Brey/Ptger2tm1Brey
either: (involves: 129S6/SvEvTac) or (involves: 129S6/SvEvTac * C57BL/6)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• treatment with PGE2 fails to increase serum calcium levels unlike in wild-type controls


Mouse Genome Informatics
hm4
    Ptger2tm1Brey/Ptger2tm1Brey
involves: 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• the renal afferent arteriolar responses to sulprostone and endothelin 1 are increased compared to wild-type controls
• norepinephrine precontracted renal afferent arterioles contract rather than dilate in response to PGE2 (1 uM ) or butaprost (1 uM) exposure
• this constriction response can be reversed by angiotensisn converting enzyme inhibition

tumorigenesis
• develop fewer lung tumors following a two stage 3-methylcholanthrene and butylated hydroxytoluene protocol
• develop smaller lung tumors following a two stage 3-methylcholanthrene and butylated hydroxytoluene protocol

homeostasis/metabolism
N
• the decrease in tumor burden is not the result of a decrease in butylated hydroxytoluene induced lung inflammation as this response is similar to wild-type controls (J:116015)
• develop fewer lung tumors following a two stage 3-methylcholanthrene and butylated hydroxytoluene protocol

muscle
• the renal afferent arteriolar responses to sulprostone and endothelin 1 are increased compared to wild-type controls
• norepinephrine precontracted renal afferent arterioles contract rather than dilate in response to PGE2 (1 uM ) or butaprost (1 uM) exposure
• this constriction response can be reversed by angiotensisn converting enzyme inhibition


Mouse Genome Informatics
hm5
    Ptger2tm1Brey/Ptger2tm1Brey
involves: 129S6/SvEvTac * BALB/c
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• LPS induced cerebral oxidative damage is reduced relative to controls

nervous system
• LPS induced cerebral oxidative damage is reduced relative to controls
• however, kainic acid induced cerebral oxidative damage is not significantly different from wild-type controls


Mouse Genome Informatics
hm6
    Ptger2tm1Brey/Ptger2tm1Brey
involves: 129S6/SvEvTac * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
N
• no defects are detected in oocyte maturation or egg fertilization, in vitro (J:69034)
• no defects are detected in implantation or decidualization (J:69034)
• at 2 to 8 months of age females produce far fewer eggs relative to wild-type females (J:69034)
• response to a superovulation protocol is better in young females (3 weeks of age) relative to older females (J:69034)
• reduced number of implantations when assessed at E5 (J:53646)
• reduced ovulation and fertilization only about 50% regardless of male genotype (J:53646)
• litter sizes from crosses of homozygous males and females were reduced

cardiovascular system
• PGE2-dependent vasodilation effects lost
• 8-16 week old females with significantly increased systolic pressure
• increased systolic pressure in males as well but not statistically significant
• reversible increase in blood pressure when placed on a high salt diet

respiratory system
• prior treatment with PGE2 fails to reduce the responsiveness to methacholine

immune system
• following infection with Pseudomonas aeruginosa (PA103) bacterial counts in the right lung are lower compared to wild-type controls

muscle
• PGE2-dependent vasodilation effects lost


Mouse Genome Informatics
cx7
    Ptger2tm1Brey/Ptger2tm1Brey
Tg(APPswe,PSEN1dE9)85Dbo/0

involves: 129S6/SvEvTac * C3H * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• at 12 months of age in males, indices of lipid peroxidation are reduced in the brain suggesting a decrease in oxidative stress relative to transgenic mice wild-type for Ptger2
• however, no difference is detected at 2 months of age prior to onset of plaque formation

other phenotype
• at 8 and 12 months of age in females and males, respectively, the levels of Abeta peptides and the amyloid plaque load are reduced relative to transgenic mice wild-type for Ptger2


Mouse Genome Informatics
cx8
    Ptger2tm1Brey/Ptger2tm1Brey
Tg(MMTV-PTGS2)#Thla/0

involves: 129S6/SvEvTac * C57BL/6 * CD-1 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
N
• unlike transgenic mice wild-type for Ptger2, 12 week old virgin females do not display precocious mammary gland development (J:98801)
• in contrast to transgenic mice wild-type for Ptger2, few multiparous females develop mammary gland hyperplasia (J:98801)


Mouse Genome Informatics
cx9
    Hrhr/Hrhr
Ptger2tm1Brey/Ptger2tm1Brey

involves: 129S6/SvEvTac * C57BL/6 * SKH1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• UVR induced tumors are more erythematous and have less keratinization
• UVR induced tumors are more likely to be poorly differentiated and deeply invasive compared to tumors in wild-type mice
• while the total number of tumors is reduced, the number of larger lesions (greater than 10 mm in diameter) is increased
• develop about half as many tumors as wild-type mice following a 15 week escalating light dose protocol

integument
• after a modest UVR exposure (180 mJ/cm2) keratinocyte proliferation is significantly lower compared to wild-type controls
• however, keratinocyte proliferation following higher levels of UVR exposure is similar to wild-type controls


Mouse Genome Informatics
cx10
    Hrhr/Hrhr
Ptger2tm1Brey/Ptger2+

involves: 129S6/SvEvTac * C57BL/6 * SKH1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
N
• unlike mice homozygous for both alleles, mice heterozygous for Ptger2tm1Brey do not show any protection against tumor formation following a 15 week escalating light dose protocol (J:117581)

integument
• after a modest UVR exposure (180 mJ/cm2) keratinocyte proliferation is significantly lower compared to wild-type controls
• however, keratinocyte proliferation following higher levels of UVR exposure is similar to wild-type controls