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Abstract: FR-PO380

Conditional Ablation of Nephrons in Fetal Mice

Session Information

Category: Development‚ Stem Cells‚ and Regenerative Medicine

  • 500 Development‚ Stem Cells‚ and Regenerative Medicine

Authors

  • Inage, Yuka, Tokyo Jikeikai Ika Daigaku, Minato-ku, Tokyo, Japan
  • Matsumoto, Kei, Tokyo Jikeikai Ika Daigaku, Minato-ku, Tokyo, Japan
  • Yamanaka, Shuichiro, Tokyo Jikeikai Ika Daigaku, Minato-ku, Tokyo, Japan
  • Matsui, Kenji, Tokyo Jikeikai Ika Daigaku, Minato-ku, Tokyo, Japan
  • Matsumoto, Naoto, Tokyo Jikeikai Ika Daigaku, Minato-ku, Tokyo, Japan
  • Saito, Yatsumu, Tokyo Jikeikai Ika Daigaku, Minato-ku, Tokyo, Japan
  • Hirano, Daishi, Tokyo Jikeikai Ika Daigaku, Minato-ku, Tokyo, Japan
  • Oishi, Kimihiko, Tokyo Jikeikai Ika Daigaku, Minato-ku, Tokyo, Japan
  • Kobayashi, Eiji, Tokyo Jikeikai Ika Daigaku, Minato-ku, Tokyo, Japan
  • Yokoo, Takashi, Tokyo Jikeikai Ika Daigaku, Minato-ku, Tokyo, Japan
Background

In humans, nephron number can vary up to ten-folds and a low nephron number is associated with an increased risk of hypertension and chronic kidney disease. Although low oxygen exposure and maternal nutritional restriction are already reported as animal models of low nephron number, these methods can also affect the development of other organs. Thus far, factors to determine the number of nephrons in a fetus remain to be clarified. Here, we established a low nephron number model, using genetically modified mice, without affecting the development of other organs.

Methods

Six2-GFP-Cre transgenic mice were crossed with C57BL/6-Gt (ROSA) 26Sor [tm1(HBEGF)Awai]/J mice (iDTR) to obtain bigenic (Six2-GFP +/+ iDTR-mice) and control offspring (Six2-GFP -/+ iDTR-mice). Diphtheria toxin was injected (0.5 ng) via the intra-amniotic route at E13.5. Subsequently, at E19.5, caesarean delivery was performed and offspring were placed in foster care. We assessed body weight, blood pressure, and nephron number and also conducted blood and urine tests.

Results

Both bigenic and control offspring displayed adequate development. Although blood pressure was not significantly different at the 12-weeks timepoint, nephron number per area in bigenic offspring decreased by approximately 50% compared to that in control offspring. Furthermore, bigenic offspring displayed higher blood urea nitrogen levels than control offspring.

Conclusion

We successfully ablated nephrons in fetal mice, approximately 50% per area. While these mice grew normally, showing no-hypertension using this protocol, additional salt loading experiments are ongoing to further refine this low nephron number model.

Funding

  • Private Foundation Support