Phenotypes associated with this allele
nervous system
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• elevated Amyloid beta in females mice
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homeostasis/metabolism
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Map2k4tm1Ctr mutation
(0 available);
any
Map2k4 mutation
(32 available)
Map2k7tm1Rjd mutation
(0 available);
any
Map2k7 mutation
(19 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation
(6 available)
Tg(Camk2a-cre/ERT2)2Gsc mutation
(1 available)
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nervous system
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• tamoxifen-treated mice develop fewer plaques than control mice expressing Tg(APPswe,PSEN1dE9)85Dbo
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• tamoxifen-treated mice exhibit fewer dystrophic neurite clusters and few isolated neurites with residual bodies compared with control mice expressing Tg(APPswe,PSEN1dE9)85Dbo
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homeostasis/metabolism
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Prnptm2Edin mutation
(7 available);
any
Prnp mutation
(150 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation
(6 available)
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mortality/aging
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N |
• unlike transgenic mice wild-type for Prnp, life span is similar to wild-type in transgenic mice null for Prnp
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behavior/neurological
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N |
• unlike transgenic mice wild-type for Prnp, spatial learning and passive avoidance behavior are similar to controls in transgenic mice null for Prnp
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nervous system
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N |
• unlike transgenic mice wild-type for Prnp, axon degeneration and synapse loss are not seen in transgenic mice null for Prnp
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• plaque burdens are minimally different from transgenic mice wild-type for Prnp
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• astrogliosis is similar to transgenic mice wild-type for Prnp
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homeostasis/metabolism
homeostasis/metabolism
behavior/neurological
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• Background Sensitivity: despite the presence of functional hemolytic complement these mice have the same rate of lethal seizures as transgenics with the non-functional DBA/2J allele
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mortality/aging
nervous system
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N |
• no significant differences are found in cortical neuron number in complement deficient versus functional transgene carriers
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• Background Sensitivity: despite the presence of functional hemolytic complement these mice have the same rate of lethal seizures as transgenics with the non-functional DBA/2J allele
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• Background Sensitivity: the complement pathway does not impact plaque deposition in the cortex, the number of plaques is the same as that in transgene carriers with the DBA/2J allele of Hc
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Itm2btm1.1Ldad mutation
(0 available);
any
Itm2b mutation
(18 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation
(6 available)
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nervous system
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• obvious increase in soluble APP-alpha in brain homogenates
• significant increase in both Abeta40 and Abeta42 compared to mice wild-type for Itm2b
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Agrntm5Jrs mutation
(0 available);
any
Agrn mutation
(101 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation
(6 available)
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nervous system
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N |
• Agrn gene is expressed primarily in CNS neurons
• no affect on amyloid beta
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lrrtm3tm1Msa mutation
(0 available);
any
Lrrtm3 mutation
(31 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation
(6 available)
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptger2tm1Brey mutation
(4 available);
any
Ptger2 mutation
(31 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation
(6 available)
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nervous system
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• 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
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homeostasis/metabolism
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Nr1h3tm1Djm mutation
(3 available);
any
Nr1h3 mutation
(32 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation
(6 available)
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nervous system
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• a significant increase in cortical the Abeta1-40 plaque number is seen in mice at 32 weeks of age compared transgenic mice on a wild-type background
• plaques are also increased in size
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homeostasis/metabolism
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Nr1h2tm1Djm mutation
(3 available);
any
Nr1h2 mutation
(26 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation
(6 available)
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nervous system
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• a significant increase in cortical the Abeta1-40 plaque number is seen in mice at 32 weeks of age compared transgenic mice on a wild-type background
• plaques are also increased in size
• there is also a significant increase in Abeta1-42 plaque number at this age
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homeostasis/metabolism
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1(H1/tetO-RNAi:Pion)Pggd mutation
(0 available);
any
Gt(ROSA)26Sor mutation
(942 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation
(6 available)
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nervous system
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• doxycycline-treated mice exhibit fewer amyloid plaques compared with un-induced mice
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homeostasis/metabolism
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rtn4rl2tm1Yanr mutation
(0 available);
any
Rtn4rl2 mutation
(24 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation
(6 available)
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nervous system
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• mice exhibit reduced amyloid plaque production compared to in Tg(APPswe,PSEN1dE9)85Dbo mice
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homeostasis/metabolism
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPswe,PSEN1dE9)85Dbo mutation
(6 available)
Tg(MGS1-19375/CFP)2R9Rwb mutation
(0 available)
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nervous system
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• decreased levels of both amyloid beta-40 and -42
• mostly insoluble forms are reduced
• decrease is significant in males but not females
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homeostasis/metabolism
homeostasis/metabolism
endocrine/exocrine glands
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• increase in beta cell mass and beta cell area compared to control Leprdb heterozygotes
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growth/size/body
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N |
• body weight is normal at 5-7 weeks of age
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Apmaptm1a(KOMP)Wtsi mutation
(0 available);
any
Apmap mutation
(19 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation
(6 available)
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behavior/neurological
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• in a simplified Morris water maze test, 20-month-old mice show a more severe spatial memory deficit with poorer escape learning during training trials and significantly less time spent in the target quadrant during the probe trial relative to age-matched transgenic mice wild-type for Apmap
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nervous system
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• 9-month-old mice show a 20 +/- 4 % increase in cerebral Abeta1-40 peptide levels associated with a 24 +/- 5 % increase in the hippocampal Abeta plaque area relative to age-matched transgenic mice wild-type for Apmap
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homeostasis/metabolism
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPswe,PSEN1dE9)85Dbo mutation
(6 available)
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nervous system
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• sparse deposits observed at 21 weeks of age, however, numerous deposits are observed at 45 and 60 weeks
(J:113199)
• deposits are more extensive in females
(J:113199)
• level of brain amyloid beta peptide 42 is predominant over 40; levels increase dramatically after 20 weeks of age
(J:113199)
• senile plaques detected by thioflavin S or the anti-amyloid beta antibody, 3D6, as early as 4 months of age
(J:113200)
• plaques are restricted to cortex and hippocampus at time points up to 12 months of age
(J:113200)
• plaques increase in number and size over time
(J:113200)
• exhibits an overall increase in soluble and insoluble amyloid beta peptide 40 and 42 between 4 and 12 months
(J:113200)
• insoluble amyloid beta42 is increased 2-fold in cerebrum of sucrose-fed mice as compared to water-fed control
(J:129021)
• total amyloid beta levels are increased by 3.6 fold in sucrose fed mice
(J:129021)
• amyloid beta deposition is increased by 2.9-fold as determined by immunohistochemical and morphometric analysis in sucrose-fed mice
(J:129021)
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• exhibits progressive increase in cerebral amyloid angiopathy as early as 6 months
• amyloid deposition is observed in leptomeningeal vasculature
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behavior/neurological
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• transgenic mice fed sucrose water failed to learn Morris water maze test after 5 days of training
• water-fed transgenic mice retained some learning ability over 5 day test period, but did not perform as well in the water maze test as non-transgenic controls
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• mice fed sucrose water exhibited increased water consumption
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homeostasis/metabolism
cardiovascular system
growth/size/body
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• mice fed sucrose water consistently gained weight over study time period (2 months- 8 months)
• sucrose-fed mice increased body weight by 17% over water-fed controls
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPswe,PSEN1dE9)85Dbo mutation
(6 available)
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Beta-amyloid plaques in Tg(APPswe,PSEN1dE9)85Dbo/0 mice and neurofibrillary tangles in Mapttm1(EGFP)Klt/Mapttm1(EGFP)Klt Tg(MAPT)8cPdav/0 mice
mortality/aging
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• about 40% of mice are lost by 12 months of age
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behavior/neurological
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• mice exhibit decreased freezing to context
• 4 month old mice infused with the specific PTEN inhibitor VO-OHpic into the brain ventricles over a period for 3-4 weeks show improvement in contextual conditioning behavior
• 4 month old mice infused with a cell-permeable PTEN-PDZ peptide over a period of 3-4 weeks into the brain ventricles show improvement in the contextual fear conditioning tests
• however, VO-OHpic treatment does not affect auditory-cued fear conditioning (hippocampal-independent task), exploratory activity or basal freezing behavior
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• severely impaired performance in a morris water maze with much longer latencies to reach a hidden platform
(J:160557)
• performance in a morris water maze declines between 3 and 12 months of age
(J:160557)
• 6 month old mutants exhibit slower visuospatial learning than control mice
(J:172426)
• in the visuospatial re-learning test performed at 9, 11, 13, 15, and 18 months of age, mutants exhibit a decrease in the speed of re-learning the task compared to controls
(J:172426)
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• mice exhibit impaired behavior in the novel object location task
• 4 month old mice infused with the specific PTEN inhibitor VO-OHpic into the brain ventricles over a period for 3-4 weeks show improvement in spatial learning tasks
• 4 month old mice infused with a cell-permeable PTEN-PDZ peptide over a period of 3-4 weeks into the brain ventricles show improvement in the novel object-location task
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• Background Sensitivity: premature death early in life eappears to result from convulsive seizures and is much less frequent on the C57BL/6J background than on the DBA/2J background
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nervous system
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• Background Sensitivity: premature death early in life eappears to result from convulsive seizures and is much less frequent on the C57BL/6J background than on the DBA/2J background
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• Background Sensitivity: there are more ThioS+ plaques in the cortex on the C57BL/6J background than on the DBA/2J background
(J:227541)
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• at 2 months of age carriers are indistinguishable from C57BL/6J controls, but at 4 months of age very small plaques are found in the cortex, and at 6 months of age plaques are evident in the cortex and hippocampus
(J:208080)
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• axon degeneration and synapse loss
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• basal synaptic transmission is lower in hippocampal slices
• VO-OHpic treatment does not rescue the lower basal synaptic transmission
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• semi-chronic treatment with VO-OHpic fully rescues LTP levels in hippocampal slices
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taste/olfaction
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N |
• mutants do not exhibit Alzheimer's disease-related impairments in olfactory performance in tests based on an operant conditioning procedure and in tests based on a habituation/dishabituation procedure
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homeostasis/metabolism
|
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPswe,PSEN1dE9)85Dbo mutation
(6 available)
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homeostasis/metabolism
nervous system
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• Background Sensitivity: when congenial on CAST/EiJ or WSB/EiJ this Tg causes increased thioflavine S positive (ThioS+) vascular amyloid deposits, indicative of cerebral amyloid angiopathy, but this is not found in congenics on the C57BL/6J or PWK/PhJ host backgrounds
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPswe,PSEN1dE9)85Dbo mutation
(6 available)
|
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homeostasis/metabolism
hematopoietic system
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• cortical staining finds a slight increase in microglia in hemizygotes compared with DBA/2J controls
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mortality/aging
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• Background Sensitivity: There is a much higher rate of premature death in hemizygotes on the DBA/2J background than on the C57BL/6J background, although hemizygotes that survive beyond 6 months of age do not have a high rate of premature death thereafter
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immune system
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• cortical staining finds a slight increase in microglia in hemizygotes compared with DBA/2J controls
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behavior/neurological
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• Background Sensitivity: on the DBA/2J background hemizygotes that die prematurely are found in a lethal seizure pose of clenched front limbs and stretched out hind limbs consistent with the audiogenic seizure-induced death inherent in DBA/2J, but the percentage of hemizygotes found dead is much higher than that in wild type DBA/2J. Consistent with wild-type DBA/2J lethal seizures, premature death is not found in hemizygotes that survive beyond 6 months of age.
• despite the increased lethal seizures, the electroconvulsive threshold is not decreased relative to DBA/2J controls
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nervous system
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N |
• no significant differences are found between hemizygotes and DBA/2J in neuron number in the three different regions of the cortex at 6 months of age, indicating no increase in neuronal cell loss, and the number of cortical astrocytes is normal
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• Background Sensitivity: on the DBA/2J background hemizygotes that die prematurely are found in a lethal seizure pose of clenched front limbs and stretched out hind limbs consistent with the audiogenic seizure-induced death inherent in DBA/2J, but the percentage of hemizygotes found dead is much higher than that in wild type DBA/2J. Consistent with wild-type DBA/2J lethal seizures, premature death is not found in hemizygotes that survive beyond 6 months of age.
• despite the increased lethal seizures, the electroconvulsive threshold is not decreased relative to DBA/2J controls
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• cortical staining finds a slight increase in microglia in hemizygotes compared with DBA/2J controls
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• Background Sensitivity: although hemizygotes do have some ThioS+ plaque deposition in the cortex, there are far fewer plaques than are found in hemizygotes on the C57BL/6J background (average 10 per section versus 58 per section)
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPswe,PSEN1dE9)85Dbo mutation
(6 available)
|
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nervous system
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N |
• striatal volume is similar in both transgenic and wild-type at either 6 or 12 months of age
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• nuclei of medium spiny stellate neurons in both 6 and 12 month old transgenics are smaller and darker than wild-type
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• numbers of neurons are reduced in striatum of 12, but not 6, month old transgenics
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• numbers of neurons are reduced in striatum of 12, but not 6, month old transgenics
• reduced neuron density is observed in striatum of 12, but not 6, month old transgenics
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homeostasis/metabolism
|
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPswe,PSEN1dE9)85Dbo mutation
(6 available)
|
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behavior/neurological
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• in the Morris water maze, 6-7 and 9-10 month old, but not 3-4 month old, mice show decreased crossing plate times in the probe trial indicating that spatial discrimination learning impairments begin at 6-7 months of age
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• in the Morris water maze, 6-7 and 9-10 month old, but not 3-4 month old, mice require longer to find the platform, indicating that spatial memory impairments begin at 6-7 months of age
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• in the buried food test, mice need more time to find the hidden food than wild-type mice indicating impaired olfactory performance
• in the olfactory discrimination test, mice show decreases in the numbers of correct olfactory discrimination responses per trial at 3-4 months, 6-7 months, and 9-10 months of age
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homeostasis/metabolism
nervous system
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• mice show a gradual increase in the amount, degree of aggregation, and spatial distribution of amyloid beta deposits from the outer to the inner layers of the olfactory bulb with increasing age
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• the dendritic spine density of granule cells is reduced in the olfactory bulb
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• mice exhibit a wider synaptic cleft in the external plexiform layer
• however, laminar organization of the olfactory bulb is normal
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• the dendritic spine density of granule cells is reduced in the olfactory bulb
• mature spine density is the same as in wild-type mice at 3-4 months of age but is decreased in 6-7 and 9-10 month old mice
• immature spine density tends to decline at 3-4 and 6-7 months of age and is reduced at 9-10 months of age
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• the presynaptic and postsynaptic membrane structures of asymmetric synapses (excitatory synapses) in the olfactory bulb are damaged
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• thickness of the postsynaptic density in olfactory bulb asymmetric synapses is thinner in 3-4, 6-7, and 9-10 month old mice
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• mice exhibit a wider synaptic cleft in the external plexiform layer of symmetric synapses
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• synaptic vesicles of olfactory bulb asymmetric synapses exhibit unclear and broken membrane structure and blurred boundaries at 6-7 and 9-10 months of age
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• mitral cells in 3-4 and 9-10 month old mice exhibit a higher spontaneous firing rate of spontaneous action potential indicating the hyperactivation of mitral cells
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• 3-4 and 9-10 month old mice exhibit increased gamma, low-gamma, and high-gamma oscillations and firing rates of mitral cells in the olfactory bulb external plexiform layer
• local application of the GABA(A)R agonist muscimol nearly abolishes the aberrant increase in gamma oscillations in the external plexiform layer at advanced stages of disease while a GABA(A)R antagonist bicuculline increased the gamma oscillations
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPswe,PSEN1dE9)85Dbo mutation
(6 available)
|
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nervous system
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• plaques are abundant in hippocampus and cortex by 9 months of age
(J:87691)
• occasional deposits can be found in mice as young as 6 months of age
(J:87691)
• ratio of amyloid beta peptide 40:42 is 0.50:1
(J:87691)
• deposits observed in hippocampus by 6 months of age
(J:139071)
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• transient long term potentiation (t-LTP) is reduced in transgenics and is age-independent
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behavior/neurological
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• transgenic mice exhibit a 4-5% higher preference for the arm of the radial arm water maze that held the platform on the previous day
• 13 month old transgenic mice commit more errors in the water maze than controls, at 7 months of age both groups test similarly
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• 14 month old transgenic mice exhibit a reduced ability to maintain balance on a rotarod
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growth/size/body
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• at 14 months, transgenics weigh less than controls
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homeostasis/metabolism
|
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPswe,PSEN1dE9)85Dbo mutation
(6 available)
|
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cardiovascular system
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• Background Sensitivity: Fibrin was detected outside the microvessels in brains sections of hemizygotes on the WSB congenic background but not on the C57BL/6J congenic background or either wildtype control
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homeostasis/metabolism
nervous system
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• Background Sensitivity: Fibrin was detected outside the microvessels in brains sections of hemizygotes on the WSB congenic background but not on the C57BL/6J congenic background or either wildtype control
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• Background Sensitivity: when congenial on CAST/EiJ or WSB/EiJ this Tg causes increased thioflavine S positive (ThioS+) vascular amyloid deposits, indicative of cerebral amyloid angiopathy, but this is not found in congenics on the C57BL/6J or PWK/PhJ host backgrounds
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Analysis Tools