Inducible Knockout of Par 1 a/b in the Kidney

Project: Research project

Project Details

Description

? DESCRIPTION (provided by applicant): This proposal involves development of a new mouse model and generation of preliminary data that will facilitate transition from the current K award t independence. Acute kidney injury (AKI) is associated with morbidity and mortality in hospitalized patients. Apico-basal polarity is required for directional transport in renal epitheli and is disrupted in AKI. Partitioning defective Par1a and 1b are serine threonine kinases that establish apico-basal polarity in cell culture, but also regulate downstream pathways that affect cell-cell adhesion, cell cycle, cell survival and other pathways that are relevant for epithelial repair. The underlying hypothesis of these studies is that Par1a/b are protective in the setting of acute kidney injury and contribute to renal epithelial repair. To test this, we will generate a mouse model for inducible kidney specific deletion of Par1a/b using CRISPR/Cas9 mediated genome engineering, and examine the effect of loss of Par1a/b on severity of acute kidney injury. In addition, we will examine the relevance of Par1a/b induction after injury, by examining expression of Par1a/b in human kidney tissue (left over, not needed for diagnosis) with pathologic evidence of AKI. The specific aims are: Aim1: Generate a model of inducible kidney specific deletion of Par1a/b. Aim2: Determine effect of Par1a/b deletion on severity of acute kidney injury in mice, and Aim3: Examine the expression of Par1a/b in human acute kidney injury.
StatusFinished
Effective start/end date3/1/1612/31/18

Funding

  • National Institute of Diabetes and Digestive and Kidney Diseases: $77,547.00

ASJC

  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Cell Biology
  • Histology
  • Developmental Biology

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