Updated 9 December 2008

General Information

Transgene: A transgenic construct of a chimeric mo/hu amyloid precursor protein (APPswe/ind) under the control of a tetracycline-responsive promoter element (TRE or tetO) was injected into fertilized C57BL/6J X C3HeJ F2 mouse eggs. Founder line 8-85 was established. Male hemizygous mice were mated to female B6C3F1/J (Stock No. 100010) mice. Generation: [?+N1p]+N4 (11-Nov-08).

Transgenic APP expression was activated by crossing the APPswe/ind mice to animals producing tTA under control of the CaMKIIα promoter (see Stock No. 003010 for example). Nearly complete suppression of the transgene can be shown by treatment with doxycycline.

Mutation: Swedish (KM570/571NL) and Indiana (V617F)

Promoter: Tetracycline-responsive promoter element (TRE or tetO)

Breeding: TJL mating systerm: Hemizygote x F1 (Female x Male)

Strain: B6C3-Tg(tetO-APPswe/ind)8-85Dbo/J

Phenotype

Neuropathological Analysis:

Tg mice express a chimeric mo/huAPP protein at 10-30 fold over endogenous levels.

When bred with another tg mouse expressing reverse tet-controlled transactivator protein (reTA) or tetracycline-controlled transactivator protein (tTA) the APPSwe/Ind tg expression can be regulated with doxycycline.

Doxycycline treatment inhibits APP expression by >95% and reduces Aβ production to levels found in non-tg mice.

Plaques in forebrain at 6 months.

Hemizygous mice are viable and fertile.

Bigenic mice were 10-fold more active during dark phase of day-night cycle.

Hyperactivity was abolished by rearing bigenic mice on doxycycline.

Availability

Terms and Conditions: This strain is not available to companies or For Profit-Entities; it is available to research institutions for non-commercial research.

Use of the Tet-System may require a license; see Licenses for Strains Using TET-System Technology.

Contact: The Jackson Lab, available, Stock # 006004.

References

Primary:

Jankowsky JL, Slunt HH, Gonzales V, Savonenko AV, Wen JC, Jenkins NA, Copeland NG, Younkin LH, Lester HA, Younkin SG, Borchelt DR. Persistent amyloidosis following suppression of Abeta production in a transgenic model of Alzheimer disease. PLoS Med. 2005 Dec;2(12):e355. Epub 2005 Nov 15 Abstract

Associated:

Borchelt DR; Davis J; Fischer M; Lee MK; Slunt HH; Ratovitsky T; Regard J; Copeland NG; Jenkins NA; Sisodia SS; Price DL. 1996. A vector for expressing foreign genes in the brains and hearts of transgenic mice. Genet Anal 13(6):159-63. Abstract