Phenotypes associated with this allele

• Allele Symbol: Tg(tetO-APPSwInd)107Dbo
• Allele Name: transgene insertion 107, David R Borchelt
• Allele ID: MGI:3708462
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-APPSwInd)107Dbo/0	(FVB/NJ x B6.Cg-Tg(tetO-APPSwInd)107Dbo Tg(Camk2a-tTA)1Mmay)F1	MGI:5478560
cx2	Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-APPSwInd)107Dbo/0	involves: C3H/HeJ * C57BL/6 * CBA	MGI:3709152

Genotype
MGI:5478560

cx1

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-APPSwInd)107Dbo/0
• Genetic Background: (FVB/NJ x B6.Cg-Tg(tetO-APPSwInd)107Dbo Tg(Camk2a-tTA)1Mmay)F1

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

behavior/neurological

behavior/neurological phenotype ( J:195259 )

♂N • bitransgenic (off-DOX) males perform like wild-type males in Plus water maze apparatus, swimming abilities, and latency to find platform

abnormal long-term spatial reference memory ( J:195259 )

♂ • in a test of long-term reference memory, radial arm water maze (RAWM) administered after a 24 hour delay, bi-transgenic males (off-DOX) performed at the level of chance with a significantly increased number of errors compared to wild type

♂ • bi-transgenic mice (on-DOX) perform similar to non-transgenic controls in RAWM

♂ • in a test of cognitive flexibility, as assessed by changing the water maze escape platform position daily, bi-transgenic males (on-DOX) continue to visit the original location significantly more frequently than non-transgenic controls, however, in subsequent sessions the error rate becomes similar to non-transgenic controls

impaired spatial working memory ( J:195259 )

♂ • 12.5 month old bi-transgenic males (off-DOX) exhibit significantly less preference for exploring the new arm of the two trial Y maze (a test of short term spatial memory)

♂ • 12.5 month old bi-transgenic males (on-DOX) exhibit a preference for the new arm

♂ • 12.5 month old bi-transgenic males (off-DOX) exhibit improved performance after successive trials, but an increased number of errors compared to wild-type non-Tg and on-DOX Tg controls in the radial arm water maze (RAWM), a test of long term spatial memory

nervous system

amyloid beta deposits ( J:195259 )

♂ • found in the CA layer of the hippocampus in off-DOX and on-DOX (for 7 days) 23 month old bi-transgenic males, however, after 5 weeks on doxycycline APP/amyloid beta (as assessed by mAb 6E10) immunoreactivity disappears

♂ • a low level of mobile, water-extractable Abeta42 is present in bitransgenic males treated with DOX for up to 4 weeks

homeostasis/metabolism

amyloid beta deposits ( J:195259 )

♂ • found in the CA layer of the hippocampus in off-DOX and on-DOX (for 7 days) 23 month old bi-transgenic males, however, after 5 weeks on doxycycline APP/amyloid beta (as assessed by mAb 6E10) immunoreactivity disappears

♂ • a low level of mobile, water-extractable Abeta42 is present in bitransgenic males treated with DOX for up to 4 weeks

Genotype
MGI:3709152

cx2

• Allelic Composition: Tg(Camk2a-tTA)1Mmay/0; Tg(tetO-APPSwInd)107Dbo/0
• Genetic Background: involves: C3H/HeJ * C57BL/6 * CBA

nervous system

amyloid beta deposits ( J:109829 )

• doxycycline-mediated suppression of transgenic APPSwInd synthesis leads to parallel reductions of amyloid beta peptide levels

• early onset amyloid formation is observed, with plaques observed as early as 8 weeks of age in mice receiving no doxycycline (DOX) treatment

• plaques are restricted to the forebrain, including the cortex, hippocampus, olfactory bulb, and striatum; by 6 months, amyloid burden covers large cortical and hippocampal areas

• first observed plaques are fibrillar-core deposits; in 6 month old animals, diffuse plaques are apparent and these are abundant at 9 months, while in 9-12 month-old mice, plaques are visible in the thalamus

• no lesions are observed in the cerebellum or brain stem

• animals receiving no treatment display moderate amyloid pathology at 6 months, which progresses to a severe amyloid burden by 9 months

• mice raised for 6 months with no (DOX) treatment, followed by 3 or 6 months of DOX treatment show similar pathology to untreated 6-month old animals, despite relatively long lesion clearance times

abnormal dentate gyrus morphology ( J:185792 )

• mice exhibit a progressive neuronal atrophy that is most pronounced in the granule cell layer of hippocampal dentate gyrus

hippocampal neuron degeneration ( J:185792 )

• mice exhibit a progressive neuronal atrophy that is most pronounced in the granule cell layer of hippocampal dentate gyrus

• however, when mice are reared on doxycycline, cell loss is not observed

neurofibrillary tangles ( J:109829 )

• first visible plaques are fibrillary-cored deposits

abnormal astrocyte morphology ( J:109829 )

• activated astrocytes are found near plaques in all affected mice glial pathology is more severe in older mice

• if transgene expression is suppressed with doxycycline treatment, pathology does not progress in severity

abnormal nervous system physiology ( J:109829 )

• mice produce transgenic APP protein at 10- to 30-fold over endogenous App levels

• sensitivity of transgene suppression by doxycycline is intermediate between mice of line 885 and line 102

CNS inflammation ( J:109829 )

• neuritic pathology is observed around plaques; neuritic pathology is more severe in older mice

• if transgene expression is suppressed with doxycycline treatment, pathology does not progress in severity

behavior/neurological

abnormal locomotor activation ( J:109829 )

• hyperactive behavior is partially reversed in some mice by 1 month of transgene suppression starting at 4-5 months of age

increased locomotor activity ( J:109829 )

• untreated mice show hyperactivity, often running in circles around the perimeter of cages

• similar patterns of activity are observed in Morris water maze, with repetitive swim patterns seen in radial water maze swim test

• hyperactive phenotype penetrance is ~100%

• untreated mice show 10-fold more ambulatory activity during the dark phase; even in light phase, activity is several-fold increased compared to wild-type controls; this activity is completely abolished in mice raised on doxycycline

abnormal circadian behavior ( J:109829 )

• all animals raised with doxycycline have altered circadian rhythms with less distinction between day- and nighttime activity levels

immune system

CNS inflammation ( J:109829 )

• neuritic pathology is observed around plaques; neuritic pathology is more severe in older mice

• if transgene expression is suppressed with doxycycline treatment, pathology does not progress in severity

homeostasis/metabolism

amyloid beta deposits ( J:109829 )

• doxycycline-mediated suppression of transgenic APPSwInd synthesis leads to parallel reductions of amyloid beta peptide levels

• early onset amyloid formation is observed, with plaques observed as early as 8 weeks of age in mice receiving no doxycycline (DOX) treatment

• plaques are restricted to the forebrain, including the cortex, hippocampus, olfactory bulb, and striatum; by 6 months, amyloid burden covers large cortical and hippocampal areas

• first observed plaques are fibrillar-core deposits; in 6 month old animals, diffuse plaques are apparent and these are abundant at 9 months, while in 9-12 month-old mice, plaques are visible in the thalamus

• no lesions are observed in the cerebellum or brain stem

• animals receiving no treatment display moderate amyloid pathology at 6 months, which progresses to a severe amyloid burden by 9 months

• mice raised for 6 months with no (DOX) treatment, followed by 3 or 6 months of DOX treatment show similar pathology to untreated 6-month old animals, despite relatively long lesion clearance times

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:109829