Podocyte-specific expression of tamoxifen-inducible Cre recombinase in mice

Hideki Yokoi1, Masato Kasahara, Masashi Mukoyama

  • 1Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Kyoto, Japan.

Abstract

Insights

Researchers developed new inducible transgenic mice for studying podocyte gene function. This tamoxifen-inducible system allows gene disruption in podocytes after birth, overcoming limitations of earlier models.

Area of Science:

  • Nephrology
  • Genetics
  • Molecular Biology

Background:

  • Podocytes are crucial for normal kidney glomerular function.
  • Existing podocyte-specific knockout mice have limitations for studying gene function in certain disease states.
  • Embryonic lethality or congenital abnormalities can hinder research with conventional models.

Purpose of the Study:

  • To develop a temporal control system for genetic manipulation in podocytes.
  • To create tamoxifen-inducible Cre recombinase transgenic mice for podocyte research.
  • To enable gene disruption in podocytes post-birth.

Main Methods:

  • Constructed NPHS2-CreER(T2) transgenic mice using a podocin promoter.
  • Crossed NPHS2-CreER(T2) mice with ROSA26 reporter mice to assess Cre activity.
  • Administered tamoxifen (4-OHT) to 4-week-old double-mutant mice.

Main Results:

  • Tamoxifen administration resulted in beta-galactosidase expression specifically in 85% of glomerular podocytes.
  • Cre recombinase mRNA expression was predominantly localized to the kidney, particularly glomeruli.
  • Demonstrated successful temporal and podocyte-specific gene targeting.

Conclusions:

  • Successfully generated podocyte-specific inducible Cre transgenic mice.
  • Tamoxifen administration enables targeted gene disruption in adult podocytes.
  • These mice are valuable tools for investigating podocyte gene function in various conditions.