General Information

Updated 22 May 2005

Transgene: PS1 knock-in mouse line was derived using a two-step mutagenesis strategy based on the creation of a targeting vector that bears base changes in the coding region at codons M233T and L235P and surrounding introns of the Ps1 gene. The mixed PS1KI were bred with APP751SL mice (see Blanchard, Wirths, Langui).

Mutation: PS1(M233T) (L235P) and APP751 London (V717I), Swedish (K670N/M671L)

Promoter: Thy1

Mouse Strain: The PS1KI line was established in both pure 129SV and mixed 129SV-C57BL/6 genetic backgrounds. The mixed PS1KI were bred with APPSL mice on a mixed C57BL/6-CBA genetic background. : C57BL/6 50%-CBA 25%-129SV 25%.

Phenotype

Neuropathological Analysis:

The bigenic mice show expected acceleration of extracellular Aβ peptide deposition, and develop an age-dependent massive neuronal loss in the hippocampus. Extensive neuronal loss in the CA1/2 subfield is seen at 10 months of age in both male and female mice with detection as early as 6 months in female mice. The neuronal loss distribution closely parallels the strong intraneuronal Aβ immunostaining and the accumulation of intracellular thioflavine-S-positive material present throughout the pyramidal cell layer but does not correlate with extracellular deposits. Strong astrogliosis is also occurring in proximity of Aβ-positive neurons. Both intraneuronal Aβ and thioflavine-S-positive material stainings preceded neuronal loss.

Behavioral:

Viable and fertile animals

Availability

Contact:
Laurent Pradier
Central Nervous System/Alzheimer program
Sanofi-Aventis Pharma Paris Research Center
13 Quai Jules Guesde
94400 Vitry, France.
Email: Laurent Pradier

Patents: None

References

Primary:

Casas C, Sergeant N, Itier J-M, Blanchard V, Wirths O, van der Kolk N, Vingtdeux V, van de Steeg E, Ret G, Canton T, Drobecq H|, Clark A, Bonici B, Delacourte A, Benavides J, Schmitz C, Tremp G, Bayer TA, Benoit P and Pradier L. Massive CA1/2 Neuronal Loss with Intraneuronal and N-Terminal Truncated Aß42 Accumulation in a Novel Alzheimer Transgenic Model. Am J Pathol. 165:1289-1300, 2004. Abstract.

Associated:

Langui, D., Girardot, N., El Hachimi, K.H., Allinquant, B., Blanchard, V., Pradier, L., and Duyckaerts, C. Subcellular Topography of Neuronal A{beta} Peptide in APPxPS1 Transgenic Mice. Am J Pathol 165: 1465-1477, 2004. Abstract.

Delatour B, Blanchard V, Pradier L, Duyckaerts C. Alzheimer pathology disorganizes cortico-cortical circuitry:direct evidence from a transgenic animal model. Neurobiol Dis. 16:41-47, 2004. Abstract.

Schmitz C, Rutten BP, Pielen A, Schafer S, Wirths O, Tremp G, Czech C, Blanchard V, Multhaup G, Rezaie P, Korr H, Steinbusch HW, Pradier L, Bayer TA. Hippocampal neuron loss exceeds amyloid plaque load in a transgenic mouse model of Alzheimer's disease. Am J Path. 164:1495-502, 2004. Abstract.

Blanchard V, Moussaoui S, Czech C, Touchet N, Bonici B, Planche M, Canton T, Jedidi I, Gohin M, Wirths O, Bayer TA, Langui D, Duyckaerts C, Tremp G, Pradier L: Time sequence of maturation of dystrophic neurites associated with Abeta deposits in APP/PS1 transgenic mice. Exp Neurol. 184:247-263, 2003. Abstract.

Wirths O, Czech C, Feldmann F, Blanchard V, Tremp G, Multhaup G, Beyreuther K, Pradier L, Bayer TA. Intraneuronal APP/Abeta trafficking and plaque formation in beta-amyloid precursor protein and presenilin-1 transgenic mice. Brain Pathol. 12:275-286, 2002. Abstract.