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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• tamoxifen-treated mice exhibit fewer dystrophic neurite clusters and few isolated neurites with residual bodies compared with control mice expressing Tg(APPswe,PSEN1dE9)85Dbo
• tamoxifen-treated mice develop fewer plaques than control mice expressing Tg(APPswe,PSEN1dE9)85Dbo

other phenotype
• 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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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 (J:160557)

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 (J:160557)

nervous system
N
• unlike transgenic mice wild-type for Prnp, axon degeneration and synapse loss are not seen in transgenic mice null for Prnp (J:160557)
• astrogliosis is similar to transgenic mice wild-type for Prnp
• plaque burdens are minimally different from transgenic mice wild-type for Prnp

other phenotype
• 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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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

other phenotype
• 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


Mouse Genome Informatics
cx5
    Nr1h2tm1Djm/Nr1h2tm1Djm
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
• 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

other phenotype
• 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 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
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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• doxycycline-treated mice exhibit fewer amyloid plaques compared with un-induced mice

other phenotype
• 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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• mice exhibit reduced amyloid plaque production compared to in Tg(APPswe,PSEN1dE9)85Dbo mice

other phenotype
• 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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
other phenotype
• 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

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

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

growth/size
N
• body weight is normal at 5-7 weeks of age (J:186924)


Mouse Genome Informatics
tg10
    Tg(APPswe,PSEN1dE9)85Dbo/0
B6.Cg-Tg(APPswe,PSEN1dE9)85Dbo/Mmjax
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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

other phenotype

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 (J:172426)

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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• exhibits progressive increase in cerebral amyloid angiopathy as early as 6 months
• amyloid deposition is observed in leptomeningeal vasculature
• 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)

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

cardiovascular system

other phenotype
• exhibits progressive increase in cerebral amyloid angiopathy as early as 6 months
• amyloid deposition is observed in leptomeningeal vasculature
• 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)

growth/size
• 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 WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
N
• striatal volume is similar in both transgenic and wild-type at either 6 or 12 months of age (J:145530)
• 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

other phenotype
• increase in circulating amyloid beta protein levels

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 (J:186924)


Mouse Genome Informatics
tg13
    Tg(APPswe,PSEN1dE9)85Dbo/0
involves: C3H/HeJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
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

other phenotype
• 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)

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
• at 14 months, transgenics weigh less than controls

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