These floxed mutant mice possess loxP sites flanking exon 9 of the Crebbp gene. This strain may be useful for generating conditional mutations in applications related to transcriptional regulation, chromatin remodeling, hematopoiesis, formation of short- and long-term memory, T cell development and tumor suppression.
Paul K. Brindle, St. Jude Children's Research Hospital
The Crebbp gene encodes the CREB binding protein and the Ep300 gene encodes the E1A binding protein p300, both of which are highly conserved coactivators that promote transcription and are important to the function of many hematopoietic transcription factors. These mice possess loxP sites on either side of exon 9 of the targeted Crebbp gene. Exon 9 encodes amino acids 608-646 of the KIX domain. Mice that are homozygous for this allele are viable and fertile. When these mutant mice are bred to mice that express Cre recombinase, resulting offspring will have exon 9 deleted in the cre-expressing tissues.
When bred to a strain with Cre recombinase expression in the mammary gland (see Stock No. 003553 for example), this mutant mouse strain may be useful in studies of T cell lymphoma.
When bred to a strain with Cre recombinase expression in T cells (see Stock No. 003802 for example), offspring exhibit decreased numbers of CD4+ T cells, an increase in double positive T cell and an increased incidence of T cell lymphomas.
A targeting vector containing a loxP site flanked Neo-HSV tk selection cassette was utilized in the construction of this mutant. This selection cassette was inserted downstream of exon 9 of the targeted gene, and another loxP site was inserted upstream of exon 9. This construct was electroporated into unspecified embryonic stem (ES) cells which were transiently transfected with a Cre recombinase vector to remove the selection cassette. Correctly targeted ES cells that had successfully undergone Cre mediated recombination and no longer retained the selection cassette but did retain the loxP-flanked exon 9 were injected into blastocysts. The resulting chimeric animals were tested for germline transmission. The mice were backcrossed to C57BL/6J for 20 generations, with female heterozygotes backcrossed to a wildtype C57BL/6J male at N11.
Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.
|Allele Name||targeted mutation 1, Jan M A van Deursen|
|Allele Type||Targeted (Conditional ready (e.g. floxed), No functional change)|
|Gene Symbol and Name||Crebbp, CREB binding protein|
|Strain of Origin||Not Specified|
|Molecular Note||A loxP recombination site was inserted in intron 8 and a floxed Neo-HSV tk selection cassette was inserted in intron 9. The selection cassette was then removed from correctly targeted ES cells by by transient expression of cre recombinase.|
When maintaining a live colony, these mice can be bred as homozygotes.
When using the CBPflox mouse strain in a publication, please cite the originating article(s) and include JAX stock #025178 in your Materials and Methods section.