Phenotypes Associated with This Genotype

Genotype
MGI:5478560

• 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