| First Author | Ge Y | Year | 2011 |
| Journal | Lab Invest | Volume | 91 |
| Issue | 1 | Pages | 85-96 |
| PubMed ID | 20680007 | Mgi Jnum | J:167190 |
| Mgi Id | MGI:4867383 | Doi | 10.1038/labinvest.2010.142 |
| Citation | Ge Y, et al. (2011) Conditional ablation of glycogen synthase kinase 3beta in postnatal mouse kidney. Lab Invest 91(1):85-96 |
| abstractText | Glycogen synthase kinase (GSK)3 is a ubiquitously expressed serine/threonine kinase existing in two isoforms, namely GSK3alpha and GSK3beta. Aside from the long-recognized role in insulin signal transduction and glycogen biosynthesis, GSK3beta has been recently coined as a master control molecule in nuclear factor-kappaB activation and inflammatory kidney injury. Nevertheless, previous studies are less conclusive because they relied greatly on small molecule inhibitors, which lack selectivity and barely distinguish between the GSK3 isoforms. In addition, early embryonic lethality after global knockout of GSK3beta precludes interrogation of the biological role of GSK3beta in the adult kidney. To circumvent these issues, the Cre/loxP system was used to generate a conditional knockout mouse model in which the GSK3beta gene was specifically deleted in kidney cortical tubules at postnatal mature stage. Kidney-specific ablation of GSK3beta resulted in a phenotype no different from control littermates. Knockout mice (KO) were viable and exhibited normal development and normal kidney physiology in terms of kidney function, urine albumin excretion, and urine-concentrating ability. It is noteworthy that apart from normal glomerular and tubulointerstitial morphology, the kidneys from KO demonstrated more glycogen accumulation in the renal cortical tubules as assessed by both periodic acid-Schiff staining for light microscopy and direct biochemical assay, consistent with an elevated glycogen synthetic activity as evidenced by diminished inhibitory phosphorylation of glycogen synthase that occurred subsequent to GSK3beta ablation. This finding was further validated by electron microscopic observations of increased deposition of glycogen particles in the renal tubules of KO, suggesting that GSK3alpha could not fully compensate for the loss of GSK3beta in regulating glycogen metabolism in the kidney. Collectively, our study suggests that kidney-specific ablation of GSK3beta barely affects kidney function and histology under normal circumstances. Extended examinations of these KO under diseased conditions are merited to understand the role of GSK3beta in renal pathophysiology. |
