Research Models

PSEN1-flox

Synonyms: PS1 conditional KO

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Species: Mouse
Genes: PSEN1
Modification: PSEN1: Knock-Out
Disease Relevance: Alzheimer's Disease
Strain Name: B6;129P-Psen1tm1Vln/J
Genetic Background: Origin: 129P2/OlaHsd; backcrossed to C57BL/6
Availability: The Jackson Lab: Stock# 007605; Cryopreserved

Summary

These floxed mice can be used to generate animals with conditional knock-out of presenilin-1. They can be crossed with strains expressing Cre recombinase to target the gene deletion to specific cell types, such as postnatal neurons (see The Jackson Lab: Stock# 006143). When bred to mice that express Cre recombinase, progeny can have one of three genotypes: only exon 7 deleted, only the neomycin selection cassette deleted, or both exon 7 and the neomycin selection cassette deleted, in the Cre-expressing cells. Mice that are homozygous for this allele are viable, fertile, normal in size, and do not display any gross physical or behavioral abnormalities.

When PS1-flox mice are crossed with those expressing Cre recombinase under the control of the Thy-1 promoter, mice with specific deficiency of PS1 in postnatal neurons are generated, PS1(n-/-). Unlike mice with complete PSEN1 deficiency, which are late embryonic lethal due to skeletal deformation, CNS hemorrhage, and deficiencies in neurogenesis and neuronal survival (Wong et al., 1997; Shen et al., 1997), PS1(n-/-) mice are born at the expected Mendelian frequency and are viable and fertile with no gross brain abnormalities or premature lethality. PS1(n−/−) mice have decreased murine Aβ40 and Aβ42 and accumulate C-terminal fragments of APP. They do not have cognitive deficits as measured by an object recognition task, but do have slightly abnormal LTP induction relative to control animals (Dewachter et al., 2002).

Modification Details

A targeting vector containing a neomycin resistance gene was inserted downstream of exon 7 of PSEN1; loxP sites were inserted on both sides of exon 7 and downstream of the neomycin resistance gene.

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References

Paper Citations

  1. . Presenilin 1 is required for Notch1 and DII1 expression in the paraxial mesoderm. Nature. 1997 May 15;387(6630):288-92. PubMed.
  2. . Skeletal and CNS defects in Presenilin-1-deficient mice. Cell. 1997 May 16;89(4):629-39. PubMed.
  3. . 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. PubMed.

External Citations

  1. The Jackson Lab: Stock# 006143
  2. The Jackson Lab: Stock# 007605

Further Reading

No Available Further Reading