B6.129S6(CBA)-Cebpa^tm1Dgt/J

Stock number: 006447
Research areas: Cancer Research, Cell Biology Research, Developmental Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Internal/Organ Research, Research Tools

Description

The C/EBPalpha "floxed" allele (C/EBPalphaF) functions similarly to the wildtype allele. These mutant mice may be useful in studying hematopoietic cell (e.g. myeloid and basophil progenitor cell) development and function, cancer (e.g. acute myeloid leukemia), and alveolar cell differentiation.

Detailed description

Mice carrying this C/EBPalpha "floxed" allele (C/EBPalphaF) are viable and fertile. The floxed allele functions similarly to the wildtype allele. In mice homozygous for C/EBPalpha^F and expressing an interferon-inducible Cre recombinase (introduced by breeding to a cre-expressing strain; see Stock No. 003556), C/EBPalpha activity is disrupted, leading to defective myeloid cell development, increased hematopoietic stem cell repopulating activity, and significantly increased myeloblast population in the bone marrow compartment. In combination with an appropriate Cre transgenic strain, these mutant mice may be useful in studies of hematopoietic cell (e.g. myeloid and basophil progenitor cell) development and function, cancer (e.g. acute myeloid leukemia), and alveolar cell differentiation.

Development

A targeting vector was designed to flank the single Cebpa exon with loxP sites. A neomycin resistance cassette was also inserted between the exon and the downstream loxP site. The targeting vector was introduced into 129S6/SvEvTac-derived TC1 embryonic stem (ES) cells. Correctly targeted cells were injected into C57BL/6 blastocysts and implanted into foster mothers. Mutant offspring were backcrossed for 9 generations to C57BL/6 mice. Prior to arrival at The Jackson Laboratory, mutant mice were crossed with "Mx1-Cre" transgenic mice also backcrossed 9 generations to C57BL/6 mice (B6.CBA genetic background, see Stock No. 006230). Upon arrival, double mutant mice were bred to C57BL/6J and the resulting offspring carrying only the C/EBPalpha^F floxed allele were selectively bred to establish this strain.

Allele

Symbol: Cebpa^tm1Dgt
Name: targeted mutation 1, Daniel G Tenen
MGI accession ID: MGI:3522010
Generation method: Targeted
Attributes: Conditional ready (e.g. floxed); No functional change
Marker symbol: Cebpa
Marker name: CCAAT/enhancer binding protein (C/EBP), alpha
Chromosome: 7
Strain of origin: 129S6/SvEvTac
Site of expression: Following 3-4.5 weeks of poly I:C treatment, deletion efficiency is greater than 95% in hematopoietic tissues, and C/EBPalpha protein is undetectable in bone marrow.
Molecular note: LoxP sites were inserted to flank the single exon and a neo cassette inserted downstream of the exon. Western blot of whole-cell lysates of adult liver and total bone marrow cells showed that protein was present in mutants.