Research Models

PS1(M146L)

Synonyms: PSEN1(M146L), PS1 (M146L) line 5.1

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Species: Mouse
Genes: PSEN1
Mutations: PSEN1 M146L (A>C)
Modification: PSEN1: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: N/A
Genetic Background: Swiss Webster x B6D2F1
Availability: Available through the Technology Transfer Office, Patents & Licensing, University of South Florida.

Summary

The first report of this transgenic line described two lines of mice that overexpress human PSEN1 with the M146L mutation, line 5.1 and line 6.2 (Duff et al., 1996). Line 5.1 has been more extensively characterized, especially in relation to the double transgenic PS/APP (Holcomb et al., 1998). In the original report, it was found that animals that overexpress mutant, but not wild-type, PSEN1, show a selective increase in brain Aβ42(43) (Duff et al., 1996).

Neuropathology

No abnormal pathology up to 2.5 years. Elevated Aβ42(43); no effect on Aβ40 (Duff et al., 1996). Altered mitochondrial activity (Begley et al., 1999). Disregulation of calcium homeostasis (Begley et al., 1999; Barrow et al., 2000).

Cognition/Behavior

No difference from non-transgenic control mice in the "Y" maze (alternation performance or activity) at 12-14 weeks (Holcomb et al., 1998).

Other Phenotypes

Elevated PSEN1 expression (2-3 fold). Medium and late after hyperpolarizations in CA3 pyramidal cells we larger compared with nontransgenic controls. Larger calcium responses to depolarization. Stronger synaptic potentiation of the CA3 to CA1 projection (Barrow et al., 2000).

Modification Details

Transgene containing human PSEN1 with the M146L mutation driven by the rat PDGF-β promoter.

Availability

Available through the Technology Transfer Office, Patents & Licensing, University of South Florida.

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References

Research Models Citations

  1. PS/APP

Paper Citations

  1. . Increased amyloid-beta42(43) in brains of mice expressing mutant presenilin 1. Nature. 1996 Oct 24;383(6602):710-3. PubMed.
  2. . Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nat Med. 1998 Jan;4(1):97-100. PubMed.
  3. . Altered calcium homeostasis and mitochondrial dysfunction in cortical synaptic compartments of presenilin-1 mutant mice. J Neurochem. 1999 Mar;72(3):1030-9. PubMed.
  4. . Functional phenotype in transgenic mice expressing mutant human presenilin-1. Neurobiol Dis. 2000 Apr;7(2):119-26. PubMed.

External Citations

  1. Technology Transfer Office, Patents & Licensing, University of South Florida.

Further Reading

No Available Further Reading