C.B6-Nuggc^tm1.2Diaz/J

Stock number: 022017
Research areas: Cancer Research, Cell Biology Research, Research Tools

Description

These Slip-GC floxed mutant mice possess loxP sites flanking exons 2-4 of the nuclear GTPase, germinal center associated (Nuggc) gene. This strain may be useful for studying the increase in G:C transitions in B lymphocytes.

Detailed description

These Slip-GC floxed mutant mice possess loxP sites flanking exons 2-4, including the highly conserved GTPase domain, of the nuclear GTPase, germinal center associated (Nuggc) gene. Nuggc is expressed in germinal center B cell lymphocytes and may protect B cells from activation-induced deaminase (AID)-dependent DNA breaks. Nuggc is highly expressed in germinal center-derived B cell lymphomas. Homozygotes are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exons 2-4 deleted in cre-expressing tissues.

For example, when crossed to Sox2-cre mice, expressing embryonic Cre recombinase in (see Stock No. 008454), Nuggc deficiency in offspring results in an increase in G:C transitions in B cells from Peyer's Patches.

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 4 of the nuclear GTPase, germinal center associated (Nuggc) gene. The construct was electroporated into C57BL/6-derived 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-exons 2-4, intact floxed-neo cassette, or excision of both exons 2-4 and the neo cassette. Correctly targeted ES cells, containing only the floxed-exons 2-4, were injected into C57BL/6 blastocysts and resulting chimeric males were bred with C57BL/6 females. Progeny were crossed to remove the Cre transgene and these Slip-GC were bred to C57BL/6J mice for at least 6 generations. Mice were then bred to BALB/c mice for at least 6 generations. Upon arrival at The Jackson Laboratory, mice were bred to BALB/cJ inbred mice (Stock No. 000651) for at least one generation to establish the colony.

Allele

Symbol: Nuggc^tm1.2Diaz
Name: targeted mutation 1.2, Marilyn Diaz
MGI accession ID: MGI:5476765
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Nuggc
Marker name: nuclear GTPase, germinal center associated
Chromosome: 14
Strain of origin: C57BL/6
Molecular note: A loxP site was inserted upstream of exon 2. A floxed neo cassette was inserted downstream of exon 4. Cre-mediated recombination removed the neo cassette and left exons 2 through 4 floxed.