title: Gα12 is required for renal cystogenesis induced by Pkd1 inactivation.
abstract: Mutation of PKD1, encoding the protein polycystin-1 (PC1), is the main cause of autosomal dominant polycystic kidney disease (ADPKD). The signaling pathways downstream of PC1 in ADPKD are still not fully understood. Here, we provide genetic evidence for the necessity of Gα12 (encoded by Gna12, hereafter Gα12) for renal cystogenesis induced by Pkd1 knockout. There was no phenotype in mice with deletion of Gα12 (Gα12-/-). Polyinosine-polycytosine (pI:pC)-induced deletion of Pkd1 (Mx1Cre+Pkd1f/fGα12+/+) in 1-week-old mice resulted in multiple kidney cysts by 9 weeks, but the mice with double knockout of Pkd1 and Gα12 (Mx1Cre+Pkd1f/fGα12-/-) had no structural and functional abnormalities in the kidneys. These mice could survive more than one year without kidney abnormalities except multiple hepatic cysts in some mice, which indicates that the effect of Gα12 on cystogenesis is kidney specific. Furthermore, Pkd1 knockout promoted Gα12 activation, which subsequently decreased cell-matrix and cell-cell adhesion by affecting the function of focal adhesion and E-cadherin, respectively. Our results demonstrate that Gα12 is required for the development of kidney cysts induced by Pkd1 mutation in mouse ADPKD.
authors: Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Yong
authors: 0000-0001-6770-1328
authors: Y
authors: Wu
authors: Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Jen X
authors: 0000-0003-4908-9459
authors: JX
authors: Xu
authors: Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Wassim
authors: 0000-0003-2266-2171
authors: W
authors: El-Jouni
authors: Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Tzongshi
authors: 0000-0003-4472-752X
authors: T
authors: Lu
authors: Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Suyan
authors: 0000-0003-2304-0219
authors: S
authors: Li
authors: Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Qingyi
authors: 0000-0002-9435-9510
authors: Q
authors: Wang
authors: Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA Renal Division, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
authors: Mei
authors: M
authors: Tran
authors: Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Wanfeng
authors: 0000-0003-3401-0023
authors: W
authors: Yu
authors: Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Maoqing
authors: M
authors: Wu
authors: Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Ivan E
authors: 0000-0002-8232-7589
authors: IE
authors: Barrera
authors: Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Joseph V
authors: JV
authors: Bonventre
authors: Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors: Jing
authors: J
authors: Zhou
authors: Renal Division, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
authors: Bradley M
authors: 0000-0002-8137-1043
authors: BM
authors: Denker
authors: Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA tqkong@gmail.com.
authors: Tianqing
authors: 0000-0001-8634-3423
authors: T
authors: Kong
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism; D021982:Cell-Matrix Junctions; D004847:Epithelial Cells / Q000378:metabolism; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism*; D017353:Gene Deletion; D055786:Gene Knockout Techniques; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008954:Models, Biological; D016891:Polycystic Kidney, Autosomal Dominant / Q000378:metabolism* / Q000473:pathology*; D022502:Stress Fibers / Q000378:metabolism; D050396:TRPP Cation Channels / Q000378:metabolism*
chemical_list: D015820:Cadherins; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D050396:TRPP Cation Channels
keywords: Cadherin; G proteins; Polycystin-1; and Polycystic kidney diseases