Updated 23 January 2009

General Information

Transgene: Neuron-specific conditional KO of PS1, denoted PS1 (n-/-) using Cre/lox technique. A "floxed" PS1 allele was constructed to contain three loxP sites and a neomycin resistance cassette (neoR) by gene targeting in embryonic stem cells. Two loxP sites flanked exon 7 of the mouse PS1 gene and the third loxP site was placed downstream of the neoR mrker. Thy-1 Cre-recombinase transgenic mice were generated. Neuron specific Thy-1 driven Cre-recombinase was assessed by crossing with LacZ reporter mice. The PS1(n-/-) mice are bi-genic mice, generated by crossing: (1) transgenic mice with a "floxed" PS1 gene containing 3 loxP sites and (2) mice with neuron-specific expression of Cre-recombinase under control of the mouse thy1-gene promoter.

Mutation: Deletion of exon 7 of the PS1 gene

Promoter: Mouse Thy1 gene promoter (driving Cre-recombinase to neurons)

Mouse Strain: B6;129P-Psen1^tm1Vln /J

Phenotype

Neuropathological Analysis:

In adult PS1 (n-/-) mice, levels of murine brain Aß40 and 42 were strongly decreased, concomitant with accumulation of amyloid precursor protein (APP) C-terminal fragments.

Behavioral:

PS1(n-/-) are viable and fertile with normal brain morphology.

Availability

The Jackson Lab, available, stock #007605. Use by companies or for-profit entities requires a license prior to shipping.

References

Primary:

Dewachter I, Reverse D, Caluwaerts N, Ris L, Kuiperi C, Van den Haute C, Spittaels K, Umans L, Serneels L, Thiry E, Moechars D, Mercken M, Godaux E, Van Leuven F. Neuronal deficiency of presenilin 1 inhibits amyloid plaque formation and corrects hippocampal long-term potentiation but not a cognitive defect of amyloid precursor protein [V717I] transgenic mice. J Neurosci. 2002 May 1;22(9):3445-53. Abstract

Associated:

Ris L, Dewachter I, Reverse D, Godaux E, Van Leuven F. Capacitative calcium entry induces hippocampal long term potentiation in the absence of presenilin-1. J Biol Chem. 2003 Nov 7;278(45):44393-9. Abstract

Van Dorpe J, Smeijers L, Dewachter I, Nuyens D, Spittaels K, Van Den Haute C, Mercken M, Moechars D, Laenen I, Kuiperi C, Bruynseels K, Tesseur I, Loos R, Vanderstichele H, Checler F, Sciot R, Van Leuven F. Prominent cerebral Amyloid Angioplathy in APP/London transgenic mice. Am J Pathol (2000) 157:1283-1298. Abstract

Moechars D, Dewachter I, Lorent K, Reversé D, Baekelandt V, Naidu A, Tesseur I, Spittaels K, Haute CV, Checler F, Godaux E, Cordell B, Van Leuven F. Early phenotypic changes in transgenic mice that overexpress different mutants of amyloid precursor protein in brain. J Biol Chem. 1999 Mar 5 ; 274 (10):6483-92. Abstract