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. 2021 May 25;22(6):e51169. doi: 10.15252/embr.202051169

Figure 4. Genetic ablation of COUP‐TFII in adult mice attenuates injury‐induced kidney fibrosis.

Figure 4

  1. Strategy of conditional knockdown of COUP‐TFII in adult mice. A LacZ knock‐in allele is inserted into the genomic COUP‐TFII locus after the second LoxP site.
  2. Activation of Cre recombinase by tamoxifen (TAM) results in COUP‐TFII deletion and the expression of LacZ reporter (detected by immunostaining of β‐galactosidase (β‐Gal, red) in the UUO mice model (n = 2). Quantification of mean of 8–10 confocal images at 200× hpf. **P < 0.01; ***P < 0.001 by paired t‐test; mean ± SD.
  3. Using heterozygous mice (F/+; Cre/+), β‐Gal+ cells (red) increased after TAM injection in UUO kidneys, and co‐localized with COUP‐TFII+ cells (green; n = 3).
  4. COUP‐TFII+ cells decreased significantly in the UUO kidney in TAM‐treated homozygous (F/F;Cre/+) mice (KO group, n = 6) compared with wild‐type littermates (WT group, n = 4). Expression of αSMA (red) and collagen 1 (yellow) are also markedly reduced. Masson Trichrome staining shows less kidney fibrosis in KO compared with WT group. Quantification of mean of 8–10 confocal images per animal at 200× hpf. **P < 0.01 by unpaired t‐test, mean ± SD.