Generation and initial characterization of FDD knock in mice

Luca Giliberto, Shuji Matsuda, Ruben Vidal, Luciano D'Adamio

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: Mutations in the integral membrane protein 2B [1], also known as BRI2 [2], a type II trans-membrane domain protein cause two autosomal dominant neurodegenerative diseases, Familial British and Danish Dementia [3]. In these conditions, accumulation of a C-terminal peptide (ABri and ADan) cleaved off from the mutated precursor protein by the pro-protein convertase furin [4], leads to amyloid deposition in the walls of blood vessels and parenchyma of the brain. Recent advances in the understanding of the generation of amyloid in Alzheimer's disease has lead to the finding that BRI2 interacts with the Amyloid Precursor Protein (APP), decreasing the efficiency of APP processing to generate Aβ [5,6,7]. The interaction between the two precursors, APP and BRI2, and possibly between Aβ and ABri or ADan, could be important in influencing the rate of amyloid production or the tendency of these peptides to aggregate. Methodology/Principal Findings: We have generated the first BRI2 Danish Knock-In (FDDKI) murine model of FDD, expressing the pathogenic decamer duplication in exon 6 of the BRI2 gene. FDDKI mice do not show any evident abnormal phenotype, with normal brain histology and no detectable amyloid deposition in blood vessel walls or parenchyma. Conclusions/Significance: This new murine mouse model will be important to further understand the interaction between APP and BRI2, and to provide insights into the molecular basis of FDD.

Original languageEnglish
Article numbere7900
JournalPLoS One
Volume4
Issue number11
DOIs
StatePublished - Nov 18 2009

Fingerprint

Amyloid beta-Protein Precursor
amyloid
Amyloid
Abrus
mice
Blood vessels
Blood Vessels
Brain
Membrane Proteins
Furin
Neurodegenerative diseases
proteins
Peptides
Histology
Protein Precursors
animal models
blood vessels
Neurodegenerative Diseases
Exons
Alzheimer Disease

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Generation and initial characterization of FDD knock in mice. / Giliberto, Luca; Matsuda, Shuji; Vidal, Ruben; D'Adamio, Luciano.

In: PLoS One, Vol. 4, No. 11, e7900, 18.11.2009.

Research output: Contribution to journalArticle

Giliberto, Luca ; Matsuda, Shuji ; Vidal, Ruben ; D'Adamio, Luciano. / Generation and initial characterization of FDD knock in mice. In: PLoS One. 2009 ; Vol. 4, No. 11.
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