Research Models

BRI-Aβ40 (BRI2-Aβ40)

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Species: Mouse
Modification: Transgenic
Disease Relevance: Alzheimer's Disease
Strain Name: B6.Cg-Tg(Prnp-ITM2B/APP695*40)1Emcg/J
Genetic Background: B6C3, backcrossed to C57BL/6J to generate congenic strain
Availability: The Jackson Lab: Stock# 007180; Cryopreserved

Modification Details

Construct encodes a fusion protein of the BRI protein and Aβ40 driven by the mouse prion promoter; Aβ40 is secreted through proteolytic cleavage of the protein at a furin cleavage site immediately preceding Aβ40.

Summary

These transgenic mice overexpress Aβ40 without overexpressing APP. They contain a fusion construct of the BRI protein (involved in amyloid deposition in Familial British Demntia (FBD) and Familial Danish Dementia (FDD) and Aβ40. Twenty-three amino acids at the C-terminal of the BRI protein were replaced with the human Aβ40 sequence in order to generate secreted Aβ40 by taking advantage of a naturally occuring furin-like cleavage site in the BRI protein. 

Hemizygous mice are viable and fertile with a normal lifespan and no obvious behavioral abnormalities. Transgene expression corresponds with the characteristic expression pattern of the mouse prion protein promoter with highest expression in cerebellar granule cells and hippocampus, followed by the cortex, pons, thalamus, and midbrain (McGowan et al., 2005). 

These mice were generated from a founder line (line 1d) that exhibited high plasma levels of Aβ40. They were maintained on a mixed B6C3 background (previously available as Jackson Lab: Stock# 006880). They were backcrossed to C57BL/6J for at least five generations to generate the congenic strain.

In contrast to the BRI-Aβ42 mice, hemizygous BRI-Aβ40 mice express high levels of Aβ40 but do not develop overt amyloid pathology or detergent-insoluble amyloid-β (McGowan et al., 2005). Hemizygous mice on a mixed background (C57/B6//C3H) have intact cognition as measured by fear conditioning at twelve and 14-17 months (Kim et al., 2013).

Related Strains

B6;C3-Tg(Prnp-ITM2B/APP695*42)A12Emcg/Mmjax Mixed background. The Jackson Lab; the JAX MMRRC Stock# 034842 (formerly Jackson Lab Stock# 007002)

Last Updated: 06 Mar 2018

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References

Paper Citations

  1. McGowan E, Pickford F, Kim J, Onstead L, Eriksen J, Yu C, Skipper L, Murphy MP, Beard J, Das P, Jansen K, DeLucia M, Lin WL, Dolios G, Wang R, Eckman CB, Dickson DW, Hutton M, Hardy J, Golde T. Abeta42 is essential for parenchymal and vascular amyloid deposition in mice. Neuron. 2005 Jul 21;47(2):191-199. PubMed.
  2. Kim J, Onstead L, Randle S, Price R, Smithson L, Zwizinski C, Dickson DW, Golde T, McGowan E. Abeta40 inhibits amyloid deposition in vivo. J Neurosci. 2007 Jan 17;27(3):627-33. PubMed.

External Citations

  1. The Jackson Lab; the JAX MMRRC Stock# 034842
  2. The Jackson Lab: Stock# 007180

Further Reading

Papers

  1. Lewis PA, Piper S, Baker M, Onstead L, Murphy MP, Hardy J, Wang R, McGowan E, Golde TE. Expression of BRI-amyloid beta peptide fusion proteins: a novel method for specific high-level expression of amyloid beta peptides. Biochim Biophys Acta. 2001 Jul 27;1537(1):58-62. PubMed.
  2. Kim J, Onstead L, Randle S, Price R, Smithson L, Zwizinski C, Dickson DW, Golde T, McGowan E. Abeta40 inhibits amyloid deposition in vivo. J Neurosci. 2007 Jan 17;27(3):627-33. PubMed.