Expression of the human MAPT, hTau-A152T variant, is regulated by the tetracycline-responsive regulatory element (tetO) in these TRE-hTau-A152T line L1 mice. When mated with a strain expressing tetracycline-controlled transactivator protein (tTA), expression of the hTau-A152T protein may be regulated with the tetracycline analog doxycycline (dox) in the double-allelic offspring. This strain may be useful in studies related to frontotemporal dementia, Alzheimer’s disease, and other neurodegenerative diseases.
Lennart Mucke, Gladstone Inst of Neurological Disease
Mice hemizygous for the hTau-A152T transgene, founder line line L1, are viable and fertile. Expression of the 1N4R isoform of human MAPT (microtubule associated protein tau) with an A152T substitution is regulated by a tetracycline operator (tetO); also called tetracycline-responsive element (TRE, TetRE) or tet-operator). When mated to a mutant strain expressing tetracycline-controlled transactivator protein (tTA), expression of mutant 1N4R isoform of human MAPT protein may be regulated with tetracycline or its analog doxycycline (dox) in the double mutant offspring. No human MAPT protein is detected in brain sections from singly transgenic mice by western blotting and immunohistochemical staining. When these line C11-1 hTau-A152T transgenic mice are crossed to CaMKII-tTA mice (see, for example, Stock No. 007004), the adult double mutant mice have a lower body weight than wildtype and single C11-1 hTau-A152T transgenic controls. Hemizygotes are viable and fertile. Homozygous viability/fertility has not been tested (June 2016).
A transgenic construct containing cDNA of the human MAPT gene encoding the 1N4R isoform, with upstream intronic sequence (from pCI-neo vector) and a Kozak sequence, and downstream bovine growth hormone polyadenylation sequence, all under the control of the tetO, tetracycline-responsive regulatory element (pTRE-Tight), was injected into fertilized C57BL/6 mouse eggs. Founder line C11-1, also known as founder line L1, was subsequently established. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) to cryopreserve embryos. To establish our live colony, cryopreserved embryos were recovered. Sperm was later cryopreserved.
|Expressed Gene||MAPT, microtubule associated protein tau, human|
|Site of Expression|
|Allele Name||transgene insertion L1, Lennart Mucke|
|Allele Type||Transgenic (Inducible, Inserted expressed sequence, Humanized sequence)|
|Allele Synonym(s)||hTau-A152T; TRE-hTau-A152T|
|Gene Symbol and Name||Tg(tetO-MAPT*A152T)L1Lms, transgene insertion L1, Lennart Mucke|
|Promoter||tetO, tet operator,|
|Expressed Gene||MAPT, microtubule associated protein tau, human|
|Strain of Origin||C57BL/6|
|Molecular Note||A transgenic construct containing cDNA of the human MAPT gene encoding the 1N4R isoform, with upstream intronic sequence (from pCI-neo vector) and a Kozak sequence, and downstream bovine growth hormone polyadenylation sequence, all under the control of the tetO, tetracycline-responsive regulatory element (pTRE-Tight). The 1N4R isoform of human MAPT (microtubule associated protein tau) contains an A152T substitution, converting GCC (Ala) at positions 454-456 to ACC (Thr). Founder line C11-1, also known as founder line L1, was established.|
When maintaining a live colony, hemizygous mice may be bred to wildtype siblings, or to C57BL/6J inbred mice (Stock No. 000664). The Donating Investigator has not attempted to make the strain homozygous.
When using the TRE-hTau-A152T L1 mouse strain in a publication, please cite the originating article(s) and include JAX stock #028979 in your Materials and Methods section.
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