B6.129S6-Bin1^tm2Gcp/J

Stock number: 021145
Research areas: Cancer Research, Cardiovascular Research, Developmental Biology Research, Neurobiology Research, Research Tools

Description

This floxed-Bin1 strain may be useful for studying the cellular and mechanical role of Bin1 in Alzheimer's disease and the attenuation of cancer.

Detailed description

These Bin1^flox mice possess loxP sites flanking exon 3 of the bridging integrator 1 (Bin1) gene. BIN1 is a nucleocytoplasmic adaptor protein, involved in phagocytosis, apoptosis, and synaptic vesicle endocytosis. BIN1 has been implicated in the development of cardiac defects and Alzheimer's disease and has been shown to attenuate many types of cancer. Homozygotes are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 3 deleted in cre-expressing tissues. Widespread deletion results in perinatal lethality due to ventricular cardiomyopathy.

When crossed to B6129-Tg(Wap-cre)11738Mam/J mice (Stock No. 003552) expressing Cre recombinase in mammary gland tissues, no long term increase in breast cancer incidence was observed in either virgin or parous animals, however, initiation with the Ras-activating carcinogen DMBA (7,12-dimethylbenz(a)anthracene) produced higher grade, more poorly differentiated mammary gland tumors.

Development

A targeting vector was designed to insert a loxP-flanked neomycin resistance (neo) cassette upstream of exon 3, and a single mutant loxP site, with a T to C point mutation, downstream of exon 3 of the bridging integrator 1 (Bin1) gene. The construct was electroporated into 129S6/SvEvTac-derived IT2 embryonic stem (ES) cells. Correctly targeted ES cells were transiently transfected with a cre expression plasmid to delete the neo cassette. Resulting ES cells contained multiple gene rearrangments; intact floxed-exon 3, intact floxed-neo cassette, or excision of both exon 3 and the neo cassette. The mutant loxP site allowed cre-recombination to favor removal of the neo cassette rather than exon 3. Correctly targeted ES cells, containing only the floxed-exon 3, were injected into C57BL/6J blastocysts and resulting chimeric males were bred with C57BL/6J females. Resulting offspring were bred to establish a colony of Bin1^flox mice. These mice were backcrossed to C57BL/6J for at least 10 generations. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

Allele

Symbol: Bin1^tm2Gcp
Name: targeted mutation 2, George C Pendergast
MGI accession ID: MGI:3512133
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Bin1
Marker name: bridging integrator 1
Chromosome: 18
Strain of origin: 129S6/SvEvTac
Molecular note: LoxP sites flank exon 3. The 3' loxP site retained in the floxed ES cell line used to generate chimeric mouse includes a point mutant which reduces the efficiency of in vivo recombination ~50%.