These Tau Tg mice express a transgene containing the human fetal tau MAPT isoform and exhibit intraneural inclusions in brain and spinal cord tissue.
Virginia M Lee, University of Pennsylvania
These transgenic mice express the human fetal tau MAPT isoform under the direction of the mouse prion protein promoter. Hyperphosphorylated, insoluble MAPT protein is widely expressed in neurons of the CNS at levels approximately ten-fold higher than the endogenous mouse counterpart. Mice homozygous for the transgenic insert die at about three months of age. In the hemizygous mice intraneural inclusions that stain positive with T14, a monoclonal antibody specific for MAPT, are observed in brain and spinal cord tissue at 1 month of age. The number of inclusions increases until 6-9 months of age. Transmission electron microscopy studies of these inclusions reveals tightly packed aggregates of randomly arranged 10-20 nm straight filaments. Mice suffer progressive, age-dependant neuronal damage, motor weakness and gliosis. These mice recapitulate key features of tauopathies and provide a model for studying the underlying mechanism of related diseases such as FTDP-17, Alzheimer's and Pick's disease.
A transgenic construct containing the mouse Prnp (prion protein) promoter and a cDNA sequence to human MAPT (fetal tau, Tau44 isoform) was used to create transgenic animals on a B6D2F1 background. These mice were crossed with B6SJLF1 mice and then crossed with B6D2F1 mice.
|Expressed Gene||MAPT, microtubule associated protein tau, human|
|Site of Expression|
|Allele Name||transgene insertion 43, Virginia M Y Lee|
|Allele Type||Transgenic (Humanized sequence, Inserted expressed sequence)|
|Gene Symbol and Name||Tg(Prnp-MAPT)43Vle, transgene insertion 43, Virginia M Y Lee|
|Promoter||Prnp, prion protein, mouse, laboratory|
|Expressed Gene||MAPT, microtubule associated protein tau, human|
|Strain of Origin||(C57BL/6 x SJL)F1|
|General Note||Three founder lines were generated - lines 7, 27 and 43. Hemizygous mice from line 27 are not viable beyond 3 months and were not characterized in J:61052. Hemizygous mice from line 7 are phenotypically similar to line 43, however inclusions in the spinal cord are smaller and less abundant than in line 43.|
|Molecular Note||A transgenic construct containing a cDNA sequence to human MAPT (fetal tau, Tau44 isoform) under the control of the mouse Prnp promtoer was used to create transgenic animals. Quantitative Western blot analysis showed hyperphosphorylated, insoluble MAPT protein to be widely expressed in neurons of the CNS at levels approximately 10 fold higher than the endogenous mouse counterpart.|
|Mutations Made By|| |
Virginia Lee, University of Pennsylvania
When maintaining a live colony, these mice are bred as as hemizygotes. Homozygous mice die at about 3 months of age. It is uncertain if homozygous males can reproduce before death. Coat color expected from breeding: Albino, Agouti, Black.
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