Research Models

CNS-restricted PS1 cKO

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Species: Mouse
Genes: PSEN1
Modification: PSEN1: Conditional Knock-out
Disease Relevance: Alzheimer's Disease
Strain Name: fPS1/fPS1Δ;Nestin-Cre (PS1 cKO)
Genetic Background: C57BL6/129
Availability: Available through Jie Shen

Modification Details

PS1 inactivation in neuronal progenitor cells (NPCs) and NPC-derived neurons and glia was achieved by crossing a floxed PS1 mouse with a Nestin-Cre transgenic. 

Summary

To create CNS-restricted PS1 conditional KO mice, a floxed fPS1 mouse (Yu et al., 2000; Yu et al., 2001) was crossed with Nestin-Cre transgenic mice, in which Cre is expressed in neural progenitor cells under the control of the Nestin promoter. In these mice, PS1 inactivation is restricted to neural progenitor cells (NPCs) and NPC-derived neurons and glia. Neural progenitor and neuronal populations in general are greatly reduced, due to premature differentiation of neural progenitor cells. These mice also exhibit reduced radial glial generation and pertubations in cortical lamination due to migration defects of late-born neurons. Early born cortical neurons migrate and position normally (Wines-Samuelson et al., 2005).

Neuropathology

Premature differentiation of neural progenitor cells results in reduced cells and neurons. 45 percent of late-born neurons fail to migrate to their appropriate positions in the superficial cortical layers.

Cognition/Behavior

Gross behavior deficits.

Other Phenotypes

Mice are small. Premature death at 2-3 months of age.

Availability

Available through Jie Shen.

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References

Paper Citations

  1. . Heterogeneous populations of ES cells in the generation of a floxed Presenilin-1 allele. Genesis. 2000 Jan;26(1) PubMed.
  2. . APP processing and synaptic plasticity in presenilin-1 conditional knockout mice. Neuron. 2001 Sep 13;31(5) PubMed.
  3. . Role of presenilin-1 in cortical lamination and survival of Cajal-Retzius neurons. Dev Biol. 2005 Jan 15;277(2) PubMed.

Other Citations

  1. Jie Shen

Further Reading

No Available Further Reading