STOCK Brap^tm1.2Yfng/J

Stock number: 038494
Product name: Brap^flox
Research areas: Cell Biology Research, Developmental Biology Research, Neurobiology Research, Research Tools

Description

Brap^flox/flox mice have loxP sites flanking exons 2-3 of the BRCA1 associated protein (Brap) gene. These mice may be useful when studying the role of BRAP in heterochromatin remodeling during neurogenesis and its effects on cortical neurogenesis.

Detailed description

Brap^flox/flox mice have loxP sites flanking exons 2-3 of the BRCA1 associated protein (Brap) gene. Brap encodes a cytoplasmic protein that regulates cytoplasmic-nuclear shuttling of its interacting proteins or proteins with a nuclear localization signal, such as BRCA1. Brap interacts with Nde1 and is involved in neural progenitor cell cycle regulation, and heterochromatin establishment and compaction during cortical neurogenesis. BRAP has been shown to play a role in human aging. Mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific cre recombinase, resulting offspring will have exons 2 and 3 removed in the cre-expressing tissues of the offspring.

When Brap^flox/flox mice are bred to Emx1-Cre mice with cre recombinase expression in neural progenitor cells (NPCs) of the dorsal telencephalon, resulting mutant mice exhibit neuroinflammation, impaired proteostasis, accelerated neurodegeneration, and substantially shortened lifespan.

Development

The Brap^flox targeting vector was designed to insert a loxP and frt site flanked neomycin resistance (neo) cassette into intron 1 of the BRCA1 associated protein (Brap) gene, and a third loxP site was inserted into intron 3. The construct was electroporated into C57BL/6-derived embryonic stem (ES) cells. Correctly targeted ES cells were injected into albino C57BL/6 blastocysts and resulting chimeric mice were further bred to FLP-expressing mice on an unknown background to remove the neo cassette. The resulting Brap^flox mice, lacking the neo cassette, were backcrossed to C57BL/6 mice from The Jackson Laboratory for at least 5 generations by the donating laboratory (see SNP note below). Upon arrival, sperm was cryopreserved. To establish our live colony, an aliquot of frozen sperm was used to fertilize C57BL/6J oocytes (Stock No. 000664).

In 2024, a 48 SNP (single nucleotide polymorphism) panel analysis, with 43 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. Many of the 43 markers throughout the genome were segregating with an unknown source. Also, 3 of the 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed genetic background.

Allele

Symbol: Brap^tm1.2Yfng
Name: targeted mutation 1.2, Yuanyi Feng
MGI accession ID: MGI:7510103
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed)
Synonyms: Brap^flox
Marker symbol: Brap
Marker name: BRCA1 associated protein
Marker synonyms: 3010002G07Rik; BRAP2; IMP; RNF52
Chromosome: 5
Strain of origin: C57BL/6
Molecular note: The targeting vector is designed to insert a loxP and FRT-flanked neomycin resistance (neo) cassette into intron 1 and a third loxP site into intron 3. Flp-mediated recombination removed the neo cassette.