These p600flox/flox mutant mice possess loxP sites flanking exon 1 of the ubiquitin protein ligase E3 component n-recognin 4 (Ubr4) gene. P600 is involved in cytoskeletal organization, membrane morphogenesis, integrin-mediated survival signaling, calcium-calmodulin signaling, and the N-end rule pathway of ubiquitin-proteasome-mediated proteolysis. Embryonic p600 is essential for liver, cardiac, and brain development. Mice that are homozygous for this allele are viable and fertile. When bred to mice that express tissue-specific Cre recombinase, resulting offspring will have exon 1 deleted in the cre-expressing tissues.
For example, when bred to B6.Cg-Tg(Sox2-cre)1Amc/J mice (Stock No. 008454) expressing Cre-recombinase under the Sox2 promoter, resulting mice die by E14.5 due to severe cardiac problems including ventricular septal defects and thin ventricular walls. Brain of the knockout mice displays thinner cortical plate with significant less Tuj1-positive neurons. Starting from E13.5, the animals display enlarged ventricles. The orientation of the mitotic spindle in cortical neural progenitors is randomized in E12.5 animals.
