B6.Cg-Tg(tetO/Prnp-MAPT*K280)530Tli/J

Stock number: 029047
Product name: TetO-TauRDΔK
Research areas: Neurobiology Research, Research Tools

Description

These transgenic TetO-TauRDΔK mice, founder line 530, express a transgene encoding a mutant four-repeat domain of human MAPT protein (Q244-E372, TauRDΔK) under the control of the mouse Prnp gene promoter and the tetO, tetracycline-responsive regulatory element. When mated to a mutant strain expressing tetracycline-controlled transactivator protein (tTA), expression of the exogenous mutant TauRDΔK protein may be regulated with the tetracycline analog doxycycline (dox) in the double mutant offspring. These mice may be useful for studying neurodegeneration, tauopathies and neurodegenerative diseases such as Alzheimer's disease.

Detailed description

The MAPT gene encodes a microtubule-associated protein that is involved in regulating microtubule assembly and stability, as well as neuron axonal polarity. Alternative splicing of the gene generates several isoforms of different lengths. Mutations in this gene have been associated with frontotemporal dementia with parkinsonism, progressive supranuclear palsy, Pick disease, Parkinson's disease, and Alzheimer's disease. These transgenic mice express a four-repeat domain of mutant human MAPT protein (Q244-E372, TauRDΔK) under the control of the mouse Prnp gene promoter and the tetO, tetracycline-responsive regulatory element (from the moPrP-tetP vector). Hemizygous mice are viable and fertile. No exogenous protein is detected in brain lysates from TetO-TauRDΔK transgenic mice by western blot analysis. When bred with another mouse expressing tetracycline-controlled transactivator protein (tTA) or reverse tetracycline-controlled transactivator protein (rtTA), TauRDΔK (Tau4RΔK) expression in the resulting double mutant offspring can be regulated with tetracycline or its analog doxycycline (dox).

Development

A transgenic construct containing sequence encoding a mutant ΔK280 four-repeat domain of human MAPT protein (Q244-E372,TauRDΔK) under the control of the mouse Prnp gene promoter and the tetO, tetracycline-responsive regulatory element (from the moPrP-tetP vector; 42-bp tet operator sequence copies followed by the constitutively active, minimal human cytomegalovirus promoter), was injected into fertilized C57BL/6 X SJL F2 mouse eggs. Founder line 530 was subsequently established. The mice were then backcrossed to C57BL/6 for eight generations. Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

Allele

Symbol: Tg(tetO/Prnp-MAPT*K280)530Tli
Name: transgene insertion 530, Tong Li
MGI accession ID: MGI:5908855
Generation method: Transgenic
Attributes: Inducible; Inserted expressed sequence; Humanized sequence
Synonyms: Tau4RdeltaK
Marker symbol: Tg(tetO/Prnp-MAPT*K280)530Tli
Marker name: transgene insertion 530, Tong Li
Chromosome: UN
Strain of origin: (C57BL/6 x SJL)F2
Expressed genes: MAPT,microtubule associated protein tau,human
Site of expression: Cortex, hippocampus, and brain stem.
Molecular note: The transgenic construct contains sequence encoding a mutant deltaK280 four-repeat domain of human MAPT protein (Q244-E372) under the control of the mouse Prnp gene promoter and the tetO, tetracycline-responsive regulatory element (from the moPrP-tetP vector; 42-bp tet operator sequence copies followed by the constitutively active, minimal human cytomegalovirus promoter). Frontotemporal dementia and parkinsonism is linked to human chromosome 17 Lysine 280 deletion (deltaK280 or K280del). The Lys280 deletion accelerates aggregation of MAPT (Tau).