Mouse Genome Informatics
cn1
    Map2k4tm1Ctr/Map2k4tm1Ctr
Map2k7tm1Rjd/Map2k7tm1Rjd
Tg(APPswe,PSEN1dE9)85Dbo/0
Tg(Camk2a-cre/ERT2)2Gsc/0

involves: C3H * C57BL/6 * FVB/N
Key:
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


Mouse Genome Informatics
cx2
    Prnptm2Edin/Prnptm2Edin
Tg(APPswe,PSEN1dE9)85Dbo/0

B6.Cg-Prnptm2Edin Tg(APPswe,PSEN1dE9)85Dbo
Key:
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


Mouse Genome Informatics
cx3
    Itm2btm1.1Ldad/Itm2b+
Tg(APPswe,PSEN1dE9)85Dbo/0

involves: 129 * C3H * C57BL/6
Key:
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


Mouse Genome Informatics
cx4
    Nr1h3tm1Djm/Nr1h3tm1Djm
Tg(APPswe,PSEN1dE9)85Dbo/0

involves: 129S6/SvEvTac * C3H * C57BL/6
Key:
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
• plaques are also increased in size
• 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


Mouse Genome Informatics
cx5
    Nr1h2tm1Djm/Nr1h2tm1Djm
Tg(APPswe,PSEN1dE9)85Dbo/0

involves: 129S6/SvEvTac * C3H * C57BL/6
Key:
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


Mouse Genome Informatics
cx6
    Ptger2tm1Brey/Ptger2tm1Brey
Tg(APPswe,PSEN1dE9)85Dbo/0

involves: 129S6/SvEvTac * C3H * C57BL/6
Key:
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


Mouse Genome Informatics
cx7
    Gt(ROSA)26Sortm1(H1/tetO-RNAi:Pion)Pggd/Gt(ROSA)26Sor+
Tg(APPswe,PSEN1dE9)85Dbo/0

involves: 129S6/SvEvTac * C3H * C57BL/6
Key:
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


Mouse Genome Informatics
cx8
    Rtn4rl2tm1Yanr/Rtn4rl2tm1Yanr
Tg(APPswe,PSEN1dE9)85Dbo/0

involves: 129S6/SvEvTac * C3H * C57BL/6 * C57BL/6J
Key:
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


Mouse Genome Informatics
cx9
    Leprdb/Lepr+
Tg(APPswe,PSEN1dE9)85Dbo/0

involves: C3H * C57BL/6 * C57BLKS/J
Key:
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


Mouse Genome Informatics
tg10
    Tg(APPswe,PSEN1dE9)85Dbo/0
B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• about 40% of mice are lost by 12 months of age

behavior/neurological
• 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)

nervous system
• axon degeneration and synapse loss

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

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease; AD 104300 J:160557 , J:172426


Mouse Genome Informatics
tg11
    Tg(APPswe,PSEN1dE9)85Dbo/0
B6C3-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax
Key:
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
• mice fed sucrose water exhibited increased water consumption
• 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

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
OMIM IDRef(s)
Alzheimer Disease 3 607822 J:113199
Alzheimer Disease; AD 104300 J:113199


Mouse Genome Informatics
tg12
    Tg(APPswe,PSEN1dE9)85Dbo/0
involves: C3H * C57BL/6
Key:
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


Mouse Genome Informatics
tg13
    Tg(APPswe,PSEN1dE9)85Dbo/0
involves: C3H/HeJ * C57BL/6J
Key:
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)

Mouse Models of Human Disease
OMIM IDRef(s)
Alzheimer Disease 3 607822 J:87691 , J:113200
Alzheimer Disease; AD 104300 J:87691 , J:113200