Phenotypes associated with this allele

• Allele Symbol: Tg(Thy1-MAPT*)30Schd
• Allele Name: transgene insertion 30, Katharina Schindowski
• Allele ID: MGI:4940070
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Mapt^tm1(EGFP)Klt/Mapt^tm1(EGFP)Klt Tg(Thy1-MAPT*)30Schd/0	involves: 129S4/SvJae * C57BL/6 * CBA	MGI:4940110
cx2	Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0 Tg(Thy1-MAPT*)30Schd/0	involves: C57BL/6 * C57BL/6J * CBA * SJL	MGI:5559229
tg3	Tg(Thy1-MAPT*)30Schd/0	involves: C57BL/6 * C57BL/6J * CBA * SJL	MGI:5559230
tg4	Tg(Thy1-MAPT*)30Schd/0	involves: C57BL/6 * CBA	MGI:4940071

Genotype
MGI:4940110

cx1

• Allelic Composition: Mapt^tm1(EGFP)Klt/Mapt^tm1(EGFP)Klt; Tg(Thy1-MAPT*)30Schd/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA

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

mortality/aging

premature death ( J:169074 )

• mice show reduced survival relative to wild-type, with almost 100% mortality observed by 16 months

• accelerated mortality is observed before 3 months of age (after 1 month of age) compared to wild-type or Tg(Thy1-MAPT*)30Schd single mutant animals

nervous system

nervous system phenotype ( J:169074 )

N • at 12 months, neuronal cell numbers are similar in the hippocampal CA1-CA3 sectors and spinal cord to those in Tg(Thy1-MAPT*)30Schd mice; volumes of brain, cortex, hippocampal formation and cervical spinal cord are similar

abnormal brain morphology ( J:169074 )

• mice show significantly increased proportion of insoluble tau protein relative to sarkosyl-soluble tau compared to Tg(Thy1-MAPT*)30Schd single mutants

• soluble tau shows decreased phosphorylation compared to single transgenics, while insoluble tau displays significantly elevated phosporylation levels

• GSK-3 kinase activation in the brain is increased compared to wild-type and single mutants

neurofibrillary tangles ( J:169074 )

• NFTs are detected in the hippocampus, cortex, subcortical areas, brainstem, and spinal cord at 12 months, while no tangles are found in wild-type or Mapt mutants

• density (number) of NFTs is significantly increased in the hippocampus (subiculum and CA1 region) compared to Tg(Thy1-MAPT*)30Schd single mutants, but is similar between lines in the spinal cord

abnormal sciatic nerve morphology ( J:169074 )

• mice display axonal loss and reduction in cross-sectional area and axon density in the sciatic nerve compared to wild-type or Mapt mutants

abnormal spinal cord morphology ( J:169074 )

• mice develop numerous pericaryal rounded inclusions in the spinal cord; these are composed to abnormal filaments mixed with abundant neurofilaments; these are more numerous than seen in single transgenics

behavior/neurological

behavior/neurological phenotype ( J:169074 )

N • in Y-maze tests, percentage of alternations observed is not significantly different from single transgenics, Mapt mutants or wild-type at 3-6 months of age

impaired coordination ( J:169074 )

• mice show a progressive motor deficit, significant from 6 to 12 months compared to wild-type or Mapt mutants; impairment is much more severe than in Tg(Thy1-MAPT*)30Schd single mutants

Genotype
MGI:5559229

cx2

• Allelic Composition: Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas/0; Tg(Thy1-MAPT*)30Schd/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * CBA * SJL

mortality/aging

premature death ( J:201809 )

• decreased survival at 10 months of age

nervous system

amyloid beta deposits ( J:201809 )

• plaque load is reduced compared to mice hemizygous for Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas alone

decreased brain weight ( J:201809 )

• at 9 months of age compared to wild-type mice and mice hemizygous for Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas alone

decreased hippocampus pyramidal cell number ( J:201809 )

• at 9 months of age

neurofibrillary tangles ( J:201809 )

• detected in the hippocampus, cortex, and spinal cord

• tangles in hippocampal neurons are composed of straight filaments with a wavy appearance and of occasional paired helical filaments

• density of tangles in the spinal cord increases strongly from 3 to 9 months of age

• density of tangles in the hippocampus and cortex is increased compared to mice hemizygous for Tg(Thy1-MAPT*)30Schd alone

• age of onset of tangles is earlier compared to mice hemizygous for Tg(Thy1-MAPT*)30Schd alone

abnormal neurite morphology ( J:201809 )

• dilated dystrophic neurites at 9 months of age

behavior/neurological

impaired coordination ( J:201809 )

• at 6 and 8 months of age compared to wild-type mice and mice hemizygous for Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas alone

• impairment is more severe than in mice hemizygous for Tg(Thy1-MAPT*)30Schd alone

growth/size/body

decreased body weight ( J:201809 )

• significant and progressive reduction in body weight starting at 6 months of age

homeostasis/metabolism

amyloid beta deposits ( J:201809 )

• plaque load is reduced compared to mice hemizygous for Tg(APPSwFlLon,PSEN1*M146L*L286V)6799Vas alone

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Alzheimer's disease		DOID:10652		J:201809

Genotype
MGI:5559230

tg3

• Allelic Composition: Tg(Thy1-MAPT*)30Schd/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * CBA * SJL

nervous system

neurofibrillary tangles ( J:201809 )

• detected in the hippocampus, cortex, and spinal cord

behavior/neurological

impaired coordination ( J:201809 )

• at 8 months of age

Genotype
MGI:4940071

tg4

• Allelic Composition: Tg(Thy1-MAPT*)30Schd/0
• Genetic Background: involves: C57BL/6 * CBA

mortality/aging

premature death ( J:169074 )

• mice show reduced survival relative to wild-type, with almost 100% mortality observed by 18 months

behavior/neurological

behavior/neurological phenotype ( J:169074 )

N • in Y-maze tests, percentage of alternations observed is not significantly different from double transgenics, Mapt mutants or wild-type at 3-6 months of age; however, number of arm entries is significantly higher than wild-type or double mutants

N • spatial working memory is not impaired

impaired coordination ( J:169074 )

• mice show a progressive motor deficit, significant at 9 and 12 months compared to wild-type or Mapt mutants

abnormal posture ( J:111982 )

• by 7-8 months of age, mice display dystonic posture

hindlimb paralysis ( J:111982 )

• by 7-8 months of age, mice have paralyzed hindlimbs

nervous system

abnormal brain morphology ( J:169074 )

• GSK-3 kinase activation in the spinal cord is increased compared to wild-type

neurofibrillary tangles ( J:169074 )

• paired helical filaments (PHFs) in the insoluble tau fraction of neurofibrillary tangles show a low level of recruitment of endogenous murine tau; major component is transgenic human tau

• NFTs are composed mainly of bundles of straight filaments with occasional twisted filaments resembling PHFs observed in AD and other tauopathies

abnormal sciatic nerve morphology ( J:169074 )

• mice display axonal loss and reduction in cross-sectional area and axon density in the sciatic nerve compared to wild-type or Mapt mutants

abnormal spinal cord morphology ( J:169074 )

• mice develop numerous pericaryal rounded inclusions in the spinal cord; these are composed to abnormal filaments mixed with abundant neurofilaments