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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Tg(APPswe,PSEN1dE9)85Dbo
transgene insertion 85, David R Borchelt
MGI:3524957
Summary 21 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
cn1
Agrntm1Rwb/Agrntm1Rwb
Tg(APPswe,PSEN1dE9)85Dbo/?
Tg(Tek-cre)1Ywa/?
involves: 129S1/Sv * 129X1/SvJ * C3H * C57BL/6 * SJL MGI:5692156
cn2
Map2k4tm1Ctr/Map2k4tm1Ctr
Map2k7tm1Rjd/Map2k7tm1Rjd
Tg(APPswe,PSEN1dE9)85Dbo/0
Tg(Camk2a-cre/ERT2)2Gsc/0
involves: C3H * C57BL/6 * FVB/N MGI:5297909
cx3
Prnptm2Edin/Prnptm2Edin
Tg(APPswe,PSEN1dE9)85Dbo/0
B6.Cg-Prnptm2Edin Tg(APPswe,PSEN1dE9)85Dbo MGI:5050418
cx4
Hc1/Hc1
Tg(APPswe,PSEN1dE9)85Dbo/0
D2.Cg-Tg(APPswe,PSEN1dE9)85Dbo MGI:5702670
cx5
Itm2btm1.1Ldad/Itm2b+
Tg(APPswe,PSEN1dE9)85Dbo/0
involves: 129 * C3H * C57BL/6 MGI:3810993
cx6
Agrntm5Jrs/Agrntm5Jrs
Tg(APPswe,PSEN1dE9)85Dbo/?
involves: 129S1/Sv * 129X1/SvJ * C3H * C57BL/6 * FVB/N MGI:5692159
cx7
Lrrtm3tm1Msa/Lrrtm3tm1Msa
Tg(APPswe,PSEN1dE9)85Dbo/0
involves: 129S1/Sv * 129X1/SvJ * C3H * C57BL/6JHsd MGI:6197029
cx8
Gt(ROSA)26Sortm1(H1/tetO-RNAi:Pion)Pggd/Gt(ROSA)26Sor+
Tg(APPswe,PSEN1dE9)85Dbo/0
involves: 129S6/SvEvTac * C3H * C57BL/6 MGI:5295743
cx9
Nr1h2tm1Djm/Nr1h2tm1Djm
Tg(APPswe,PSEN1dE9)85Dbo/0
involves: 129S6/SvEvTac * C3H * C57BL/6 MGI:4359167
cx10
Ptger2tm1Brey/Ptger2tm1Brey
Tg(APPswe,PSEN1dE9)85Dbo/0
involves: 129S6/SvEvTac * C3H * C57BL/6 MGI:4834862
cx11
Nr1h3tm1Djm/Nr1h3tm1Djm
Tg(APPswe,PSEN1dE9)85Dbo/0
involves: 129S6/SvEvTac * C3H * C57BL/6 MGI:4359165
cx12
Rtn4rl2tm1Yanr/Rtn4rl2tm1Yanr
Tg(APPswe,PSEN1dE9)85Dbo/0
involves: 129S6/SvEvTac * C3H * C57BL/6 * C57BL/6J MGI:5292071
cx13
Tg(APPswe,PSEN1dE9)85Dbo/?
Tg(MGS1-19375/CFP)2R9Rwb/?
involves: C3H * C57BL/6 * C57BL/6J MGI:5692162
cx14
Leprdb/Lepr+
Tg(APPswe,PSEN1dE9)85Dbo/0
involves: C3H * C57BL/6 * C57BLKS/J MGI:5435319
cx15
Apmaptm1a(KOMP)Wtsi/Apmaptm1a(KOMP)Wtsi
Tg(APPswe,PSEN1dE9)85Dbo/0
involves: C57BL/6J * C57BL/6N MGI:6368112
tg16
Tg(APPswe,PSEN1dE9)85Dbo/0 B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax MGI:3665286
tg17
Tg(APPswe,PSEN1dE9)85Dbo/0 B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax MGI:5008418
tg18
Tg(APPswe,PSEN1dE9)85Dbo/0 D2.Cg-Tg(APPswe,PSEN1dE9)85Dbo MGI:5701399
tg19
Tg(APPswe,PSEN1dE9)85Dbo/0 involves: C3H * C57BL/6 MGI:3837130
tg20
Tg(APPswe,PSEN1dE9)85Dbo/0 involves: C3H/HeH * C57BL/6JNju MGI:6314698
tg21
Tg(APPswe,PSEN1dE9)85Dbo/0 involves: C3H/HeJ * C57BL/6J MGI:3663751


Genotype
MGI:5692156
cn1
Allelic
Composition
Agrntm1Rwb/Agrntm1Rwb
Tg(APPswe,PSEN1dE9)85Dbo/?
Tg(Tek-cre)1Ywa/?
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C3H * C57BL/6 * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Agrntm1Rwb mutation (1 available); any Agrn mutation (4 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation (8 available)
Tg(Tek-cre)1Ywa mutation (4 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• elevated Amyloid beta in females mice

homeostasis/metabolism
• elevated Amyloid beta in females mice




Genotype
MGI:5297909
cn2
Allelic
Composition
Map2k4tm1Ctr/Map2k4tm1Ctr
Map2k7tm1Rjd/Map2k7tm1Rjd
Tg(APPswe,PSEN1dE9)85Dbo/0
Tg(Camk2a-cre/ERT2)2Gsc/0
Genetic
Background
involves: C3H * C57BL/6 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Map2k4tm1Ctr mutation (0 available); any Map2k4 mutation (23 available)
Map2k7tm1Rjd mutation (0 available); any Map2k7 mutation (5 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation (8 available)
Tg(Camk2a-cre/ERT2)2Gsc mutation (1 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• tamoxifen-treated mice develop fewer plaques than control mice expressing Tg(APPswe,PSEN1dE9)85Dbo
• tamoxifen-treated mice exhibit fewer dystrophic neurite clusters and few isolated neurites with residual bodies compared with control mice expressing Tg(APPswe,PSEN1dE9)85Dbo

homeostasis/metabolism
• tamoxifen-treated mice develop fewer plaques than control mice expressing Tg(APPswe,PSEN1dE9)85Dbo




Genotype
MGI:5050418
cx3
Allelic
Composition
Prnptm2Edin/Prnptm2Edin
Tg(APPswe,PSEN1dE9)85Dbo/0
Genetic
Background
B6.Cg-Prnptm2Edin Tg(APPswe,PSEN1dE9)85Dbo
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Prnptm2Edin mutation (7 available); any Prnp mutation (96 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation (8 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
N
• unlike transgenic mice wild-type for Prnp, life span is similar to wild-type in transgenic mice null for Prnp

behavior/neurological
N
• unlike transgenic mice wild-type for Prnp, spatial learning and passive avoidance behavior are similar to controls in transgenic mice null for Prnp

nervous system
N
• unlike transgenic mice wild-type for Prnp, axon degeneration and synapse loss are not seen in transgenic mice null for Prnp
• plaque burdens are minimally different from transgenic mice wild-type for Prnp
• astrogliosis is similar to transgenic mice wild-type for Prnp

homeostasis/metabolism
• plaque burdens are minimally different from transgenic mice wild-type for Prnp




Genotype
MGI:5702670
cx4
Allelic
Composition
Hc1/Hc1
Tg(APPswe,PSEN1dE9)85Dbo/0
Genetic
Background
D2.Cg-Tg(APPswe,PSEN1dE9)85Dbo
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hc1 mutation (7 available); any Hc mutation (38 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation (8 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• 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

behavior/neurological
• 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

mortality/aging

nervous system
N
• no significant differences are found in cortical neuron number in complement deficient versus functional transgene carriers
• 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
• 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




Genotype
MGI:3810993
cx5
Allelic
Composition
Itm2btm1.1Ldad/Itm2b+
Tg(APPswe,PSEN1dE9)85Dbo/0
Genetic
Background
involves: 129 * C3H * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Itm2btm1.1Ldad mutation (0 available); any Itm2b mutation (4 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation (8 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• obvious increase in soluble APP-alpha in brain homogenates
• significant increase in both Abeta40 and Abeta42 compared to mice wild-type for Itm2b




Genotype
MGI:5692159
cx6
Allelic
Composition
Agrntm5Jrs/Agrntm5Jrs
Tg(APPswe,PSEN1dE9)85Dbo/?
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C3H * C57BL/6 * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Agrntm5Jrs mutation (0 available); any Agrn mutation (4 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation (8 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
N
• Agrn gene is expressed primarily in CNS neurons
• no affect on amyloid beta




Genotype
MGI:6197029
cx7
Allelic
Composition
Lrrtm3tm1Msa/Lrrtm3tm1Msa
Tg(APPswe,PSEN1dE9)85Dbo/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C3H * C57BL/6JHsd
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Lrrtm3tm1Msa mutation (0 available); any Lrrtm3 mutation (16 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation (8 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
N
• mice exhibit normal amyloid-beta production




Genotype
MGI:5295743
cx8
Allelic
Composition
Gt(ROSA)26Sortm1(H1/tetO-RNAi:Pion)Pggd/Gt(ROSA)26Sor+
Tg(APPswe,PSEN1dE9)85Dbo/0
Genetic
Background
involves: 129S6/SvEvTac * C3H * C57BL/6
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 (512 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation (8 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• doxycycline-treated mice exhibit fewer amyloid plaques compared with un-induced mice

homeostasis/metabolism
• doxycycline-treated mice exhibit fewer amyloid plaques compared with un-induced mice




Genotype
MGI:4359167
cx9
Allelic
Composition
Nr1h2tm1Djm/Nr1h2tm1Djm
Tg(APPswe,PSEN1dE9)85Dbo/0
Genetic
Background
involves: 129S6/SvEvTac * C3H * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Nr1h2tm1Djm mutation (3 available); any Nr1h2 mutation (5 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation (8 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• 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

homeostasis/metabolism
• 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




Genotype
MGI:4834862
cx10
Allelic
Composition
Ptger2tm1Brey/Ptger2tm1Brey
Tg(APPswe,PSEN1dE9)85Dbo/0
Genetic
Background
involves: 129S6/SvEvTac * C3H * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ptger2tm1Brey mutation (1 available); any Ptger2 mutation (24 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation (8 available)
phenotype observed in females
phenotype observed in males
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

homeostasis/metabolism
• 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




Genotype
MGI:4359165
cx11
Allelic
Composition
Nr1h3tm1Djm/Nr1h3tm1Djm
Tg(APPswe,PSEN1dE9)85Dbo/0
Genetic
Background
involves: 129S6/SvEvTac * C3H * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Nr1h3tm1Djm mutation (3 available); any Nr1h3 mutation (9 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation (8 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• 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

homeostasis/metabolism
• 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




Genotype
MGI:5292071
cx12
Allelic
Composition
Rtn4rl2tm1Yanr/Rtn4rl2tm1Yanr
Tg(APPswe,PSEN1dE9)85Dbo/0
Genetic
Background
involves: 129S6/SvEvTac * C3H * C57BL/6 * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rtn4rl2tm1Yanr mutation (0 available); any Rtn4rl2 mutation (13 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation (8 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• mice exhibit reduced amyloid plaque production compared to in Tg(APPswe,PSEN1dE9)85Dbo mice

homeostasis/metabolism
• mice exhibit reduced amyloid plaque production compared to in Tg(APPswe,PSEN1dE9)85Dbo mice




Genotype
MGI:5692162
cx13
Allelic
Composition
Tg(APPswe,PSEN1dE9)85Dbo/?
Tg(MGS1-19375/CFP)2R9Rwb/?
Genetic
Background
involves: C3H * C57BL/6 * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPswe,PSEN1dE9)85Dbo mutation (8 available)
Tg(MGS1-19375/CFP)2R9Rwb mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• decreased levels of both amyloid beta-40 and -42
• mostly insoluble forms are reduced
• decrease is significant in males but not females

homeostasis/metabolism
• decreased levels of both amyloid beta-40 and -42
• mostly insoluble forms are reduced
• decrease is significant in males but not females




Genotype
MGI:5435319
cx14
Allelic
Composition
Leprdb/Lepr+
Tg(APPswe,PSEN1dE9)85Dbo/0
Genetic
Background
involves: C3H * C57BL/6 * C57BLKS/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Leprdb mutation (12 available); any Lepr mutation (83 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation (8 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• nonfasting blood glucose levels are elevated compared to control Leprdb heterozygotes
• however, fasting blood glucose is normal at 5-7 weeks of age
• nonfasting and fasting hyperinsulinemia
• elevation in nonfasting plasma cholesterol levels
• however, fasting cholesterol levels are normal
• mutants exhibit decreased insulin sensitivity
• mutants exhibit an increase in expression of amyloid beta protein in plasma compared to Leprdb heterozygotes, however they do not show amyloid beta plaques yet at 5-7 weeks of age

endocrine/exocrine glands
• increase in beta cell mass and beta cell area compared to control Leprdb heterozygotes

growth/size/body
N
• body weight is normal at 5-7 weeks of age




Genotype
MGI:6368112
cx15
Allelic
Composition
Apmaptm1a(KOMP)Wtsi/Apmaptm1a(KOMP)Wtsi
Tg(APPswe,PSEN1dE9)85Dbo/0
Genetic
Background
involves: C57BL/6J * C57BL/6N
Cell Lines EPD0133_1_G06
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Apmaptm1a(KOMP)Wtsi mutation (0 available); any Apmap mutation (1 available)
Tg(APPswe,PSEN1dE9)85Dbo mutation (8 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• 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

nervous system
• 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

homeostasis/metabolism
• 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




Genotype
MGI:3665286
tg16
Allelic
Composition
Tg(APPswe,PSEN1dE9)85Dbo/0
Genetic
Background
B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPswe,PSEN1dE9)85Dbo mutation (8 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• 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)
• exhibits progressive increase in cerebral amyloid angiopathy as early as 6 months
• amyloid deposition is observed in leptomeningeal vasculature

behavior/neurological
• 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
• mice fed sucrose water exhibited increased water consumption

homeostasis/metabolism
• fasting plasma insulin levels are increased 3 fold in mice fed sucrose water as compared to water-fed control
• total cholesterol, but not HDL, levels are increased 30% in mice fed sucrose water as compared to water-fed control
• elevated plasma triglyceride levels observed in females at 15 weeks of age
• mice fed sucrose water displayed an impaired glucose tolerance as compared to water-fed control
• 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)
• exhibits progressive increase in cerebral amyloid angiopathy as early as 6 months
• amyloid deposition is observed in leptomeningeal vasculature

cardiovascular system

growth/size/body
• 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

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
Alzheimer's disease DOID:10652 J:113199
Alzheimer's disease 3 DOID:0110042 OMIM:607822
J:113199




Genotype
MGI:5008418
tg17
Allelic
Composition
Tg(APPswe,PSEN1dE9)85Dbo/0
Genetic
Background
B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPswe,PSEN1dE9)85Dbo mutation (8 available)
phenotype observed in females
phenotype observed in males
N normal phenotype

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
• about 40% of mice are lost by 12 months of age

behavior/neurological
• 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
• 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)
• 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
• 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

nervous system
• 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
• Background Sensitivity: there are more ThioS+ plaques in the cortex on the C57BL/6J background than on the DBA/2J background (J:227541)
• 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)
• axon degeneration and synapse loss
• basal synaptic transmission is lower in hippocampal slices
• VO-OHpic treatment does not rescue the lower basal synaptic transmission
• semi-chronic treatment with VO-OHpic fully rescues LTP levels in hippocampal slices

taste/olfaction
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

homeostasis/metabolism
• Background Sensitivity: there are more ThioS+ plaques in the cortex on the C57BL/6J background than on the DBA/2J background (J:227541)
• 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)

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
Alzheimer's disease DOID:10652 J:160557 , J:172426 , J:234430




Genotype
MGI:5701399
tg18
Allelic
Composition
Tg(APPswe,PSEN1dE9)85Dbo/0
Genetic
Background
D2.Cg-Tg(APPswe,PSEN1dE9)85Dbo
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPswe,PSEN1dE9)85Dbo mutation (8 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• 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)

hematopoietic system
• cortical staining finds a slight increase in microglia in hemizygotes compared with DBA/2J controls

mortality/aging
• 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

immune system
• cortical staining finds a slight increase in microglia in hemizygotes compared with DBA/2J controls

behavior/neurological
• 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

nervous system
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
• 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
• cortical staining finds a slight increase in microglia in hemizygotes compared with DBA/2J controls
• 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)

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
Alzheimer's disease DOID:10652 J:227541




Genotype
MGI:3837130
tg19
Allelic
Composition
Tg(APPswe,PSEN1dE9)85Dbo/0
Genetic
Background
involves: C3H * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPswe,PSEN1dE9)85Dbo mutation (8 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
N
• striatal volume is similar in both transgenic and wild-type at either 6 or 12 months of age
• nuclei of medium spiny stellate neurons in both 6 and 12 month old transgenics are smaller and darker than wild-type
• numbers of neurons are reduced in striatum of 12, but not 6, month old transgenics
• 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

homeostasis/metabolism
N
• mutants exhibit normal body weight, blood glucose, plasma insulin levels, nonfasting blood glucose and nonfasting plasma insulin, and normal glucose and insulin tolerance, indicating normal glucose homeostasis and insulin sensitivity
• increase in circulating amyloid beta protein levels




Genotype
MGI:6314698
tg20
Allelic
Composition
Tg(APPswe,PSEN1dE9)85Dbo/0
Genetic
Background
involves: C3H/HeH * C57BL/6JNju
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPswe,PSEN1dE9)85Dbo mutation (8 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• 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
• 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
• 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

homeostasis/metabolism
• 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

nervous system
• 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
• the dendritic spine density of granule cells is reduced in the olfactory bulb
• mice exhibit a wider synaptic cleft in the external plexiform layer
• however, laminar organization of the olfactory bulb is normal
• 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
• the presynaptic and postsynaptic membrane structures of asymmetric synapses (excitatory synapses) in the olfactory bulb are damaged
• thickness of the postsynaptic density in olfactory bulb asymmetric synapses is thinner in 3-4, 6-7, and 9-10 month old mice
• mice exhibit a wider synaptic cleft in the external plexiform layer of symmetric synapses
• 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
• 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
• 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

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
Alzheimer's disease DOID:10652 J:275175




Genotype
MGI:3663751
tg21
Allelic
Composition
Tg(APPswe,PSEN1dE9)85Dbo/0
Genetic
Background
involves: C3H/HeJ * C57BL/6J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(APPswe,PSEN1dE9)85Dbo mutation (8 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
nervous system
• 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)
• transient long term potentiation (t-LTP) is reduced in transgenics and is age-independent

behavior/neurological
• 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
• 14 month old transgenic mice exhibit a reduced ability to maintain balance on a rotarod

growth/size/body
• at 14 months, transgenics weigh less than controls

homeostasis/metabolism
• 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)





Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB), Gene Ontology (GO)
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last database update
02/18/2020
MGI 6.14
The Jackson Laboratory