Genome Toxicity and Impaired Stem Cell Function after Conditional Activation of CreER^T2 in the Intestine.

ABSTRACT: With the tamoxifen-inducible CreER^T2 system, genetic recombination can be temporally controlled in a cell-type-specific manner in intact animals, permitting dissection of the molecular underpinnings of mammalian physiology. Here we present a significant drawback to CreER^T2 technology for analysis of intestinal stem cells. Using the intestine-specific Villin-CreER^T2 mouse strain, we observed delayed intestinal regeneration post irradiation. Villin-CreER^T2 activation was associated with DNA damage and cryptic loxP site cleavage. Analysis of stem cell-specific CreER^T2 strains showed that the genome toxicity impairs function of crypt base columnar stem cells, resulting in loss of organoid initiating activity. Importantly, the stem cell imp

SUBMITTER: Bohin N 

PROVIDER: S-EPMC6294112 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature