Phenotypes associated with this allele

• Allele Symbol: Tg(Thy1-APPSwDutIowa)BWevn
• Allele Name: transgene insertion B, William E Van Nostrand
• Allele ID: MGI:3721992
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Apoe^tm2(APOE*3)Mae/Apoe^tm2(APOE*3)Mae Tg(Thy1-APPSwDutIowa)BWevn/?	involves: 129P2/OlaHsd * C57BL/6	MGI:4355225
cx2	Apoe^tm3(APOE*4)Mae/Apoe^tm3(APOE*4)Mae Tg(Thy1-APPSwDutIowa)BWevn/?	involves: 129P2/OlaHsd * C57BL/6	MGI:4355230
cx3	Nos2^tm1Lau/Nos2^tm1Lau Tg(Thy1-APPSwDutIowa)BWevn/?	involves: C57BL/6	MGI:3829507
tg4	Tg(Thy1-APPSwDutIowa)BWevn/0	involves: C57BL/6	MGI:3722063

Genotype
MGI:4355225

cx1

• Allelic Composition: Apoe^{tm2(APOE*3)Mae}/Apoe^{tm2(APOE*3)Mae}; Tg(Thy1-APPSwDutIowa)BWevn/?
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

nervous system

abnormal astrocyte morphology ( J:136318 )

• increased number of neuroreactive astrocytes in cortex

• decreased number of neuroreactive astrocytes in thalamic region

abnormal microglial cell morphology ( J:136318 )

• increased number of neuroreactive microglia in cortex

• decreased number of neuroreactive microglia in thalamic region

amyloid beta deposits ( J:136318 )

• plaque deposition in cortical parenchyma increased 20%

• reduced deposition in cerebral microvasculature

• microglia are tightly associated with parenchymal plaque amyloid

hematopoietic system

abnormal microglial cell morphology ( J:136318 )

• increased number of neuroreactive microglia in cortex

• decreased number of neuroreactive microglia in thalamic region

immune system

abnormal microglial cell morphology ( J:136318 )

• increased number of neuroreactive microglia in cortex

• decreased number of neuroreactive microglia in thalamic region

homeostasis/metabolism

amyloid beta deposits ( J:136318 )

• plaque deposition in cortical parenchyma increased 20%

• reduced deposition in cerebral microvasculature

• microglia are tightly associated with parenchymal plaque amyloid

cellular

abnormal astrocyte morphology ( J:136318 )

• increased number of neuroreactive astrocytes in cortex

• decreased number of neuroreactive astrocytes in thalamic region

abnormal microglial cell morphology ( J:136318 )

• increased number of neuroreactive microglia in cortex

• decreased number of neuroreactive microglia in thalamic region

Genotype
MGI:4355230

cx2

• Allelic Composition: Apoe^{tm3(APOE*4)Mae}/Apoe^{tm3(APOE*4)Mae}; Tg(Thy1-APPSwDutIowa)BWevn/?
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

nervous system

abnormal astrocyte morphology ( J:136318 )

• increased number of neuroreactive astrocytes in cortex

• decreased number of neuroreactive astrocytes in thalamic region

abnormal microglial cell morphology ( J:136318 )

• increased number of neuroreactive microglia in cortex

• decreased number of neuroreactive microglia in thalamic region

amyloid beta deposits ( J:136318 )

• plaque deposition in cortical parenchyma increased 20%

• reduced deposition in cerebral microvasculature

• microglia are tightly associated with parenchymal plaque amyloid

hematopoietic system

abnormal microglial cell morphology ( J:136318 )

• increased number of neuroreactive microglia in cortex

• decreased number of neuroreactive microglia in thalamic region

immune system

abnormal microglial cell morphology ( J:136318 )

• increased number of neuroreactive microglia in cortex

• decreased number of neuroreactive microglia in thalamic region

homeostasis/metabolism

amyloid beta deposits ( J:136318 )

• plaque deposition in cortical parenchyma increased 20%

• reduced deposition in cerebral microvasculature

• microglia are tightly associated with parenchymal plaque amyloid

cellular

abnormal astrocyte morphology ( J:136318 )

• increased number of neuroreactive astrocytes in cortex

• decreased number of neuroreactive astrocytes in thalamic region

abnormal microglial cell morphology ( J:136318 )

• increased number of neuroreactive microglia in cortex

• decreased number of neuroreactive microglia in thalamic region

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:136318

Genotype
MGI:3829507

cx3

• Allelic Composition: Nos2^tm1Lau/Nos2^tm1Lau; Tg(Thy1-APPSwDutIowa)BWevn/?
• Genetic Background: involves: C57BL/6

nervous system

increased neuron apoptosis ( J:132221 )

amyloid beta deposits ( J:132221 , J:143551 )

• amyloid beta deposits in the hippocampus, in the subiculum and thalamus (J:132221)

• deposits are observed by 52 weeks of age (J:143551)

abnormal brain interneuron morphology ( J:143551 )

• 65% loss of NPY interneurons in the hippocampus

abnormal hippocampus CA3 region morphology ( J:132221 , J:143551 )

• thinning of the CA3 and subiculum, with a 40% loss of neurons in the CA3 region (J:132221)

• neuronal loss (J:143551)

decreased subiculum size ( J:132221 , J:143551 )

• 35% loss of neurons in the subiculum (J:132221)

• neuronal loss (J:143551)

tau protein deposits ( J:132221 )

• mice show intraneuronal aggregrates of tau

• hyperphosphorylated tau is seen in the brain and in neuronal processes associated with blood vessels

decreased neuron number ( J:143551 )

• neuronal loss is observed in hippocampus, subiculum and CA3

neurodegeneration ( J:132221 )

• 30% loss of NeuN-immunopositive neurons in the hippocampus, 35% loss in the subiculum, and 40% loss in the CA3 region of the hippocampus

• loss of neuropeptide Y-immunopositive neurons particularly in the CA3 region and in the subiculum

hippocampal neuron degeneration ( J:132221 )

• 30% loss of neurons in the hippocampus

• 50% reduction in neuropeptide Y-immunopositive neurons overall throughout the hippocampus, a 65% reduction in the CA3 region, and 50% reduction in the subiculum

homeostasis/metabolism

amyloid beta deposits ( J:132221 , J:143551 )

• amyloid beta deposits in the hippocampus, in the subiculum and thalamus (J:132221)

• deposits are observed by 52 weeks of age (J:143551)

behavior/neurological

abnormal spatial reference memory ( J:132221 )

• mice make more errors in the radial-arm water maze than single Tg(Thy1-APPSwDutIowa)BWevn transgenics, especially on subsequent days, indicating slowed learning and/or retrieval of the task

• mice show increased impaired performance on the Barnes maze compared to single Tg(Thy1-APPSwDutIowa)BWevn transgenics

cellular

increased neuron apoptosis ( J:132221 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:132221

Genotype
MGI:3722063

tg4

• Allelic Composition: Tg(Thy1-APPSwDutIowa)BWevn/0
• Genetic Background: involves: C57BL/6

nervous system

abnormal astrocyte morphology ( J:124911 )

• astrocyte numbers and density are enhanced in thalamic and cortical regions where fibrillar amyloid beta deposits are prominent

abnormal microglial cell physiology ( J:124911 )

• activation of microglial and astrocytes is elevated in cortex

• microglial cells show significantly increased levels of complement proteins C1q, C3 and C4

amyloid beta deposits ( J:89848 , J:124911 )

• over the course of 1 year, progressive and robust accumulation of insoluble amyloid beta-40 and -42 peptides is observed in mouse brains; increase in peptides is first observed at 3 months and increases markedly by 12 months (J:89848)

• soluble and insoluble amyloid beta-40 peptide levels are 10-fold higher than amyloid beta-42 peptide levels (J:89848)

• amyloid beta deposits are observed in the regions of the subiculum, hippocampus, and cortex at ~3 months; by ~6 months deposits become more numerous and appear in the olfactory bulb and thalamic region as well, with deposits throughout most of the forebrain by 12 months (J:89848)

• parenchymal amyloid deposits mainly present as diffuse, plaque-like deposits, with occasional deposits having a more compact structure suggesting a fibrillar nature (J:89848)

• deposits are largely in parenchyma and in diffuse form in cortex (J:124911)

cerebral amyloid angiopathy ( J:89848 , J:124911 )

• levels of amyloid beta-40 and -42 peptides are 12- and 14-fold higher in forebrain microvessels than in whole forebrain homogenates at 12 months of age; at ~3 months, levels in vasculature of forebrains is higher than whole forebrain tissue (J:89848)

• vascular amyloid beta accumulation is prominent in the thalamus and subiculum, and increases with age such that 45-55% of vessels are affected at 12 months of age; at ~6 months of age, amyloid beta deposits in and around microvessels in the thalamus and subiculum are observed (J:89848)

• microvascular amyloid beta accumulations are mainly fibrillar (J:89848)

• some arterioles in these brain regions show strong vascular and perivascular amyloid beta depostion, while blood vessel-rich regions like the hippocampal fissure show large accumulations of perivascular amyloid beta (J:89848)

• evidence of microhemorrhage is observed in microvessels with amyloid beta deposits (J:89848)

• microvascular fibrillar amyloid beta accumulation is observed in thalamic and hippocampal regions (J:124911)

immune system

abnormal microglial cell physiology ( J:124911 )

• activation of microglial and astrocytes is elevated in cortex

• microglial cells show significantly increased levels of complement proteins C1q, C3 and C4

cardiovascular system

abnormal blood circulation ( J:119251 )

• reduced cerebral blood flow, CBF, response (21% increase) to whisker stimulation is observed relative to controls (38% increase) at 9 months

• with myocardin gene transfer, CBF response drops to 10% in transgenic mice, a decrease of 50%, while it increased to 27% with shSRF gene transfer compared to 19% in shGFP controls

hematopoietic system

abnormal microglial cell physiology ( J:124911 )

• activation of microglial and astrocytes is elevated in cortex

• microglial cells show significantly increased levels of complement proteins C1q, C3 and C4

homeostasis/metabolism

amyloidosis ( J:89848 )

• mutants show decreased clearance of the mutant form of amyloid beta peptides compared to wild-type amyloid beta

amyloid beta deposits ( J:89848 , J:124911 )

• over the course of 1 year, progressive and robust accumulation of insoluble amyloid beta-40 and -42 peptides is observed in mouse brains; increase in peptides is first observed at 3 months and increases markedly by 12 months (J:89848)

• soluble and insoluble amyloid beta-40 peptide levels are 10-fold higher than amyloid beta-42 peptide levels (J:89848)

• amyloid beta deposits are observed in the regions of the subiculum, hippocampus, and cortex at ~3 months; by ~6 months deposits become more numerous and appear in the olfactory bulb and thalamic region as well, with deposits throughout most of the forebrain by 12 months (J:89848)

• parenchymal amyloid deposits mainly present as diffuse, plaque-like deposits, with occasional deposits having a more compact structure suggesting a fibrillar nature (J:89848)

• deposits are largely in parenchyma and in diffuse form in cortex (J:124911)

cerebral amyloid angiopathy ( J:89848 , J:124911 )

• levels of amyloid beta-40 and -42 peptides are 12- and 14-fold higher in forebrain microvessels than in whole forebrain homogenates at 12 months of age; at ~3 months, levels in vasculature of forebrains is higher than whole forebrain tissue (J:89848)

• vascular amyloid beta accumulation is prominent in the thalamus and subiculum, and increases with age such that 45-55% of vessels are affected at 12 months of age; at ~6 months of age, amyloid beta deposits in and around microvessels in the thalamus and subiculum are observed (J:89848)

• microvascular amyloid beta accumulations are mainly fibrillar (J:89848)

• some arterioles in these brain regions show strong vascular and perivascular amyloid beta depostion, while blood vessel-rich regions like the hippocampal fissure show large accumulations of perivascular amyloid beta (J:89848)

• evidence of microhemorrhage is observed in microvessels with amyloid beta deposits (J:89848)

• microvascular fibrillar amyloid beta accumulation is observed in thalamic and hippocampal regions (J:124911)

cellular

abnormal astrocyte morphology ( J:124911 )

• astrocyte numbers and density are enhanced in thalamic and cortical regions where fibrillar amyloid beta deposits are prominent

abnormal microglial cell physiology ( J:124911 )

• activation of microglial and astrocytes is elevated in cortex

• microglial cells show significantly increased levels of complement proteins C1q, C3 and C4

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:89848
cerebral amyloid angiopathy		DOID:9246		J:89848