Ubiquitous expression of Akt1 p.(E17K) results in vascular defects and embryonic lethality in mice.

ABSTRACT: Proteus syndrome is a progressive overgrowth disorder with vascular malformations caused by mosaic expression of the AKT1 c.49G > A, p.(E17K) activating variant which was predicted to cause lethality if expressed ubiquitously. To test that hypothesis, we used the ACTB-Cre gene to activate a conditional Akt1 p.(E17K) allele in the mouse. No offspring that was heterozygous for both Cre and the conditional allele (βA-Akt1WT/flx) was viable. Fewer than expected numbers of βA-Akt1WT/flx embryos were seen beginning at E11.5, but a few survived until E17.5. The phenotype ranged from mild to severe, but generally βA-Akt1WT/flx embryos had fewer visible blood vessels and more hemorrhages than their wild-type littermates, which was suggestive of a vascular abnormality. Examination of E13.5 limb skin

SUBMITTER: Lindhurst MJ 

PROVIDER: S-EPMC7871364 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature