B6N.Cg-Tg(Prnp-MAPT*P301S)PS19Vle/J

Stock number: 024841
Research areas: Neurobiology Research

Description

The PS19 mouse model harbors the T34 isoform of microtubule-associated protein tau with one N-terminal insert and four microtubule binding repeats (1N4R) encoding the human P301S mutation, all driven by the mouse prion protein promoter. These mice are useful in studying neurofibrillary tangles, neurodegenerative tauopathy and Alzheimer's disease.

Detailed description

PS19 transgenic mice (P301S Tg mice) express the P301S mutant form of human microtubule-associated protein tau (MAPT), under the direction of the mouse prion protein promoter (Prnp). The expression of the mutant human MAPT is five-fold higher than the expression of the endogenous mouse MAPT protein. Hyperphosphorylated, insoluble mutant human MAPT protein in the brain accumulates with age causing decreased microtubule binding.

The donating laboratory confirmed the following phenotype for these C57BL/6-congenic PS19 transgenic mice [March 2014]:
Transgenic mice have a median lifespan between 11 and 15 months. 13 week old mice are hyperactive and exhibit decreased anxiety-like behavior. By 6 months of age, motor weakness is observed. Transgenic mice have lowered thresholds in nociceptive response (hot plate test) and startle response (prepulse inhibition), as well as memory deficits. Histological analysis reveals phosphorylated tau accumulation in the lateral globus pallidus, amygdala, auditory cortex, and ventral hippocampus. Onset of neuronal loss occurs at approximately nine months of age. Transgenic mice on the congenic C57BL/6 are less variable than transgenic mice on the mixed B6;C3 background in the onset of hyperphosphorylated tau inclusions, neuronal loss, and death.
Note that Takeuchi et al. 2011 PLoS One 6:e21050 describes PS19 transgenic mice N10 onto C57BL/6J, whereas Stock No. 024841 is N7+ onto C57BL/6N (see strain Development section).

These mice cannot be bred to homozygosity as homozygous females do not mate.

Development

The P301S transgene was designed with the P301S mutant human microtubule-associated protein tau (MAPT*P301S) under the direction of the mouse prion protein promoter (Prnp). This transgene was injected into fertilized B6C3F1 mouse eggs. Transgenic founder animals were bred to B6C3F1/J or B6C3F1/Crl mice to establish founder line 19 (PS19). The resulting PS19 colony was maintained in a hemizygous fashon on the B6C3F1 background, and then backcrossed to C57BL/6J for 10 generations. The mice were then maintained by crossing transgenic males to to C57Bl/6NCrl females for 7 generations. During backcrossing, the Y chromosome was not fixed to the C57Bl/6NCrl genetic background. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6NJ (Stock No. 005304) at least once to establish the colony.

Allele

Symbol: Tg(Prnp-MAPT*P301S)PS19Vle
Name: transgene insertion PS19, Virginia M Y Lee
MGI accession ID: MGI:3768407
Generation method: Transgenic
Attributes: Inserted expressed sequence; Humanized sequence
Marker symbol: Tg(Prnp-MAPT*P301S)PS19Vle
Marker name: transgene insertion PS19, Virginia M Y Lee
Chromosome: 3
Strain of origin: (C57BL/6 x C3H)F1
Expressed genes: MAPT,microtubule associated protein tau,human
Molecular note: The transgene construct contains the P301S mutant human microtubule-associated protein tau, MAPT, under the direction of the mouse prion protein, Prnp, promoter. The expression of the mutant human MAPT is 5-fold higher than the expression of the endogenous mouse Mapt protein. Transgene insertion occurred on Chr 3, causing a 249 Kb deletion.