These Ep300 knock-out mice exhibit embryonic lethality with defects in neurulation, cell proliferation and heart development. They are suitable for use in applications related to the study of transcriptional coactivators and may be useful in studies related to human Rubinstein–Taybi syndrome (RTS).
David M. Livingston, Dana-Farber Cancer Institute
Mice that are homozygous null for the Ep300 gene are embryonic lethal, dying between embryonic days 9 and 11.5 exhibiting defects in neurulation, cell proliferation and heart development. Isolated embryonic fibroblasts display a proliferation defect, growing much slower and for fewer generations than embryonic fibroblasts derived from wild type embryos. Mice heterozygous for the null allele also exhibit a degree of embryonic lethality, a trait apparently influenced by genetic background. The highest lethality in heterozygotes is observed on a 129 background, with considerably less seen on a mixed B6;129 background and none on an incipient congenic C57BL/6 background.
A targeting vector containing a neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter was used to disrupt three exons encoding the first Cys/His domain of the Ep300 gene. A herpes simplex virus thymidine kinase was used for negative selection. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric animals were backcrossed to C57BL/6 mice.
|Allele Name||targeted mutation 1, David Livingston|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Ep300, E1A binding protein p300|
|Strain of Origin||129S4/SvJae|
|Molecular Note||A genomic fragment containing exons encoding the first cys/his rich domain were replaced with a neomycin selection cassette. Western blot analysis on embryonic fibroblasts derived from homozygous E10.5 embryos demonstrated that no detectable protein was expressed.|
|Mutations Made By|| |
Andrew Kung, Columbia University
This strain originated on a B6;129 background and has been backcrossed to C57BL/6 for at least 6 generations(5/2001).
When using the p300- mouse strain in a publication, please cite the originating article(s) and include JAX stock #004067 in your Materials and Methods section.