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.
Virginia M Lee, University of Pennsylvania
These 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/density. At three months of age, transgenic mice exhibit clasping and limb retraction when lifted by the tail, which progresses to limb weakness. By ten months of age the mice exhibit a hunched back and paralysis, followed by inability to feed. Transgenic mice have a median lifespan of approximately nine months with approximately 80% dying by 12 months. Histological analysis reveals neuron degeneration in hippocampus and ventricular dilatation (brain atrophy) by eight months of age, although significant neuron degeneration in the hippocampus occurs at approximately nine months of age. Neuron loss spreads to the amygdala, neocortex and entorhinal cortex by 12 months of age. Defective translocation of endoplasmic reticulum proteins in affected neurons is observed as early as three months of age. The onset of neurofibrillay tangle formation in the neocortex, amygdala, hippocampus, brain stem and spinal cord is five months of age. Transgenic mice display neuroinflammation with microglial activation and astrogliosis. The ultrastructure of the neurofibrillay tangle-like lesions detected is similar to that found in brain lesions of human Alzheimer's disease and tauopathy patients. Degradation of synaptic function is significant by six months of age. These mice cannot be bred to homozygosity as homozygous females do not mate.
The phenotype of PS19 transgenic mice described above is based on the published information available as of 2008. In 2012-2013, publications using PS19 mice on a B6C3F1 or B6C3 genetic background report attenuated formation of tau pathology (hyperphosphorylated tau inclusions prominent by 12 months of age, significant neuronal death after 12 months of age), as well as males developing tau pathology more consistently than females. It is not determined if these phenotype differences are observed for the PS19 colony at The Jackson Laboratory. To ensure genetically stability, we periodically rederive our colony onto the hybrid B6C3F1/J genetic background (Stock No. 100010). This was last performed in August 2013.
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 as hemizygotes on the B6C3F1 background before sending to The Jackson Laboratory Repository in 2008.
|Expressed Gene||MAPT, microtubule associated protein tau, human|
|Site of Expression|
|Allele Name||transgene insertion PS19, Virginia M Y Lee|
|Allele Type||Transgenic (Humanized sequence, Inserted expressed sequence)|
|Allele Synonym(s)||P301S tau (line PS19); PS19 Tg|
|Gene Symbol and Name||Tg(Prnp-MAPT*P301S)PS19Vle, transgene insertion PS19, Virginia M Y Lee|
|Gene Synonym(s)||P301S tau (line PS19); PS19 Tg|
|Promoter||Prnp, prion protein, mouse, laboratory|
|Expressed Gene||MAPT, microtubule associated protein tau, human|
|Strain of Origin||(C57BL/6 x C3H)F1|
|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.|
|Mutations Made By|| |
Virginia Lee, University of Pennsylvania
When maintaining a live colony, these mice can be bred as hemizygotes. These mice cannot be bred to homozygosity as homozygous females do not mate.
|Please inquire about possible genotypes.|
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of
each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders
are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in
order to provide the minimum number of animals, animals will ship within 25 weeks.
The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.
MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.
In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of, PRODUCTS or SERVICES, JACKSON will, at its option, provide credit or replacement for the PRODUCT received or the SERVICES provided; JACKSON makes no other representations and this shall be the exclusive remedy of the purchaser. Please note specific policy for live mice.
Consistent with the requirement for a written understanding regarding animal care and use, the JACKSON Animal Care and Use Committee will review the animal care and use protocol(s) associated with any SERVICES to be performed at JACKSON, and JACKSON shall have ultimate responsibility and authority for the care of animals while on site or in JACKSON custody.
In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.
MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.
The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.
Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.