| First Author | Tanaka K | Year | 2024 |
| Journal | PLoS One | Volume | 19 |
| Issue | 5 | Pages | e0303910 |
| PubMed ID | 38805434 | Mgi Jnum | J:350367 |
| Mgi Id | MGI:7644783 | Doi | 10.1371/journal.pone.0303910 |
| Citation | Tanaka K, et al. (2024) Dach1 is essential for maintaining normal mature podocytes. PLoS One 19(5):e0303910 |
| abstractText | Dach1 is highly expressed in normal podocytes, but this expression rapidly disappears after podocyte injury. To investigate the role of Dach1 in podocytes in vivo, we analyzed global, podocyte-specific, and inducible Dach1 knockout mice. Global Dach1 knockout (Dach1-/-) mice were assessed immediately after birth because they die within a day. The kidneys of Dach1-/- mice were slightly smaller than those of control mice but maintained a normal structure and normal podocyte phenotypes, including ultrastructure. To study the role of Dach1 in mature podocytes, we generated Dach1 knockout mice by mating Dach1fl/fl mice with Nphs1-Cre or ROSA-CreERT2 mice. Due to inefficient Cre recombination, only a small number of podocytes lacked Dach1 staining in these mice. However, all eleven Nphs1-Cre/Dach1fl/fl mice displayed abnormal albuminuria, and seven (63%) of them developed focal segmental glomerulosclerosis. Among 13 ROSA-CreERT2/Dach1fl/fl mice, eight (61%) exhibited abnormal albuminuria after treatment with tamoxifen, and five (38%) developed early sclerotic lesions. These results indicate that while Dach1 does not determine the fate of differentiation into podocytes, it is indispensable for maintaining the normal integrity of mature podocytes. |
