Sustained cell proliferation of renal epithelial cells in mice with inv mutation

Abstract

A tubule system is an important component of the nephron, which is the structural and functional unit of the kidney. Expansion of renal tubules results in renal cysts. Hereditary forms of renal cystic diseases suggest that tubular size is determined genetically. The inv was discovered as a mutant with renal cysts and situs inversus . Inv / inv , inv∆ ∆ ∆ ∆ C::GFP ( inv∆ ∆ ∆ ∆ C) mouse was created by the introduction of the inv gene lacking the C-terminus ( inv∆ ∆ ∆ ∆ C) into inv / inv mice. The mouse develops multiple renal cysts without situs abnormality, giving us an opportunity to study inv function in renal tubular structure maintenance. In the present study, we showed that inv suppresses cyst progression in a dose-dependent manner and that the inv∆ ∆ ∆ ∆ C cystic kidneys showed increased cell proliferation and apoptosis. Cell cycle regulators for G1-S progression were activated in the cystic kidney. Furthermore, cDNA microarray and semiquantitative RT-PCR analysis showed that growth-related genes maintained a high level of expression in the cystic kidney at 4 weeks of age whereas they were decreased in control kidneys, suggesting that cells in inv∆ ∆ ∆ ∆ C kidney are still active in the cell cycle. One of the inv protein functions may provide a stop signal for renal epithelial cell proliferation.

Renal-Retinal Ciliopathy Gene Sdccag8 Regulates DNA Damage Response Signaling

“…3 Our histologic analysis of the kidneys showed that Sdccag8 gt/gt mice displayed a classic nephronophthisis phenotype at P100, with the cystic dilations originating from the DCTs and CCDs. Compared with other mouse models of nephronophthisis, [22][23][24][25] the onset of the renal phenotype in Sdccag8 gt/gt mice occurred relatively late. The process of cyst formation appeared to coincide with interstitial fibrosis that surrounded the glomeruli and nephrons.…”

Blockade of Death Ligand TRAIL Inhibits Renal Ischemia Reperfusion Injury

“…Proteins from homogenized total renal tissue were analyzed by western blotting using antibodies against Caspase-8 (Santa Cruz Biotechnology, Inc., CA) and actin (Cell Signaling Biotechnology, Beverly, MA) as described previously [37]. Three kidneys were used for one experiment group, and data were collected by three independent experiments.…”

Mouse models of ciliopathies: the state of the art

“…Additional roles in cardiac morphogenesis, independent of global L-R asymmetry determination, have also been argued (McQuinn et al, 2001). Furthermore, kidneys of Invs inv mutant mice exhibit defects including cyst formation and a delay in tubular maturation (Yokoyama et al, 1993; Sugiyama and Yokoyama, 2006). The early lethality of this mouse mutant detracts from its utility as a model, although it has proven to be an excellent tool.…”