B6.C(Cg)-Grb2^tm1.1Lnit/J

Stock number: 020422
Research areas: Cell Biology Research, Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

These Grb2 floxed mice may be useful for studying the effect of GRB2-dependant signal transduction on lymphocyte differentiation and immune response.

Detailed description

These Grb2 floxed mice possess loxP sites flanking exon 2 of the growth factor receptor bound protein 2 (Grb2) gene. Grb2 encodes an adaptor protein involved in signal transduction from cell surface growth factor receptors and mediates Ras, Raf, and ERK1/2 activation. Exon 2 encodes part of the first SH3 domain and its deletion leads to a non-functional GRB2 protein. Homozygotes are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 2 deleted in the cre-expressing tissues.

For example, when crossed to a strain expressing a B-cell specific Cre recombinase, GRB2 deficient mice have reduced numbers of immature and mature follicular B cells in peripheral lymphoid organs due to a differentiation block and decreased B-cell survival. They also exhibit enhanced BCR-induced Ca2⁺ signaling, abnormal MAPK activation patterns, and impaired Akt PI3K signaling.

Development

A targeting vector was designed to insert a loxP site followed by a frt-flanked neomycin resistance (neo) cassette upstream of exon 2, and a second loxP site downstream of exon 2 of the growth factor receptor bound protein 2 (Grb2) gene. The construct was electroporated into BALB/cJ-derived BALB/c-I embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and resulting chimeric males were bred to BALB/c females. These mice were bred to FLP transgenic mice to remove the neo, and they were subsequently bred to C57BL/6 mice for at least 10 generations. Upon arrival, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to breed out the cre allele.

Allele

Symbol: Grb2^tm1.1Lnit
Name: targeted mutation 1.1, Lars Nitschke
MGI accession ID: MGI:5568397
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Grb2
Marker name: growth factor receptor bound protein 2
Chromosome: 11
Strain of origin: BALB/cJ
Molecular note: An FRT-flanked neo cassette with a 5' loxP site was inserted upstream of exon 2. An additional loxP site was inserted downstream of exon 2. FLP-mediated recombination removed the FRT-flanked neo cassette.