Posted 27 May 2008

General Information

Transgene: 10-nucleotide duplication (TTTAATTTGT) was introduced in the BRI2 complementary DNA (cDNA) sequence by PCR, and the resulting BRI2795InsTTTAATTTGT cDNA sequence was PCR-amplified using oligonucleotide primers containing an XhoI site, a Kozak consensus sequence and a stop codon. The BRI2795InsTTT AATTTGT cDNA was inserted into the pBS/MoPrP.Xho vector and microinjected into hybrid C3HeB/FeJ mouse embryos.

Mutation: Familial Danish dementia (FDD) form of BRI2

Promoter: Mouse prion protein promoter

Mouse strain: Hybrid C3HeB/FeJ mouse embryos

Background strain: Background C57BL/6J, 10 generations

Colony Maintenance: Cross transgenic animals to non-transgenic C57BL/6J

Phenotype

Neuropathological Analysis:

Widespread cerebral amyloid angiopathy (CAA) (~7 months), parenchymal ADan deposition, vascular amyloid deposition, amyloid associated gliosis, intracellular and extracellular deposition of oligomeric forms of ADan, tau immunoreactive deposits in neuropil. No NFTs.

Behavioral Phenotype:

Aged (~1year) animals show abnormal grooming behavior, an arched back and walk with a wide-based gait and shorter steps.

Availability

Contact: Ruben Vidal, Dept of Pathology and Laboratory Medicine, Indiana Univ. School of Med, 635 Barnhill Drive MSB A136, Indianapolis, IN 46202, Phone: (317) 274-1729, Fax: (317) 278-6613, E-mail: rvidal@iupui.edu

References

Primary:

Vidal R, Barbeito AG, Miravalle L, Ghetti B. Cerebral Amyloid Angiopathy and Parenchymal Amyloid Deposition in Transgenic Mice Expressing the Danish Mutant Form of Human BRI(2). Brain Pathol. 2008 Apr 10; Abstract