Conditional gene recombination by adenovirus-driven Cre in the mouse uterus

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Adenovirus-mediated Genetic Removal of Signaling Molecules in Cultured Primary Mouse Embryonic Fibroblasts

Published on: September 9, 2010

Haibin Wang1, Huirong Xie, Hao Zhang

  • 1Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2678, USA.

Genesis (New York, N.Y. : 2000)
|January 18, 2006
PubMed

Insights

This study shows that small volumes of ADV-Cre virus target uterine epithelial cells for gene editing without affecting pregnancy. Larger volumes or different delivery methods can target stromal cells and other organs, impacting pregnancy outcomes.

Area of Science:

  • Reproductive Biology
  • Molecular Biology
  • Genetics

Background:

  • Cre-mediated gene targeting is effective in many tissues.
  • Uterine gene recombination in heterogeneous cell types using Cre activation is not well-established.

Purpose of the Study:

  • To establish methods for Cre-mediated gene recombination in the mouse uterus.
  • To investigate the effects of different ADV-Cre delivery methods on uterine cells and pregnancy.

Main Methods:

  • Utilized recombinant adenoviruses expressing Cre (ADV-Cre) and ROSA26 reporter mice.
  • Administered ADV-Cre intraluminally in small (10 microl) and large (50 microl) volumes.
  • Administered ADV-Cre intravenously on days 5-6 of pregnancy.
  • Assessed gene recombination (lacZ expression) and effects on uterine architecture and pregnancy outcomes.

Main Results:

  • Small-volume intraluminal ADV-Cre targeted uterine luminal epithelial cells, causing lacZ expression without affecting pregnancy.
  • Large-volume intraluminal ADV-Cre damaged the epithelium, induced recombination in stromal cells, and disrupted pregnancy.
  • Intravenous ADV-Cre targeted decidualizing stromal cells and showed activity in liver, spleen, ovary, and adrenal cortex.
  • Conditional gene targeting in uterine cells is feasible at specific times and physiological states.

Conclusions:

  • ADV-Cre delivery methods can be optimized for specific uterine cell targeting.
  • Uterine gene targeting strategies can be developed for various physiological states.
  • This approach offers potential for studying uterine function and treating reproductive disorders.

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