B6.129(Cg)-Itm2b^tm1Ldad/J

Stock number: 018132
Product name: BRI2^f
Research areas: Mouse/Human Gene Homologs, Neurobiology Research, Research Tools

Description

These BRI2^f/f mice possess loxP sites flanking exon 2 of the Itm2b gene and may have applications in studies related to dementia and Alzheimer's Disease.

Detailed description

These BRI2^f/f floxed mutant mice possess loxP sites flanking exon 2 of the targeted integral membrane protein 2B (Itm2b) gene. The accumulation of cleaved amyloid β-peptide (Aβ) precursor proteins (APP) form amyloid plaques in the brains of patients with familial dementias such as Alzheimer's disease. BRI2 is a membrane protein which binds to APP. When over-expressed, BRI2 inhibits the accumulation of Aβ in vitro. Also, mutations in BRI2 are associated with familial British dementia (FBD) and familial Danish dementia (FDD). Homozygous BRI2^f/f mice are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 2 deleted in cre-expressing tissues, abolishing gene expression. BRI2 deficiency results in severe hippocampal memory deficits.

Development

A targeting vector was designed to insert a single loxP site upstream of exon 2 and a loxP-flanked neomycin resistance (neo) cassette downstream of exon 2 of the integral membrane protein 2B (Itm2b) gene. The construct was electroporated into 129-derived embryonic stem (ES) cells and correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting offspring were backcrossed to C57BL/6J mice for a few generations to build a colony of BRI2^t/+ mice. These mice were then bred to Meu40-cre mice (on a C57BL/6 background), which express a mosaic cre-recombinase upon doxacycline administration, to delete the neo cassette. Resulting mice contained multiple gene rearrangments; intact floxed-exon 2, intact floxed-neo cassette, or excision of both exon 2 and the neo cassette. Offspring containing only floxed-exon 2 were bred with C57BL/6J mice to establish a colony of floxed BRI2^f/+ mice. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation.

Allele

Symbol: Itm2b^tm1Ldad
Name: targeted mutation 1, Luciano D'Adamio
MGI accession ID: MGI:3810986
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Itm2b
Marker name: integral membrane protein 2B
Chromosome: 14
Strain of origin: 129
Molecular note: A loxP site was inserted 200 bp 5' of exon 2 and a floxed PGK-neo cassette was inserted in intron 2 via homologous recombination. The floxed PGK-neo cassette was deleted via in vivo Cre-mediated recombination, leaving exon 2 floxed.