Lack of Wdr13 gene in mice leads to enhanced pancreatic beta cell proliferation, hyperinsulinemia and mild obesity.
WD-repeat proteins are very diverse, yet these are structurally related proteins that participate in a wide range of cellular functions. WDR13, a member of this family, is conserved from fishes to humans and localizes into the nucleus. To understand the in vivo function(s) of Wdr13 gene, we have created and characterized a mutant mouse strain lacking this gene. The mutant mice had higher serum insulin levels and increased pancreatic islet mass as a result of enhanced beta cell proliferation. While a known cell cycle inhibitor, p21, was downregulated in the mutant islets, over expression of WDR13 in the pancreatic beta cell line (MIN6) resulted in upregulation of p21, accompanied by retardation of cell proliferation. We suggest that WDR13 is a novel negative regulator of the pancreatic beta cell proliferation. Given the higher insulin levels and better glucose clearance in Wdr13 gene deficient mice, we propose that this protein may be a potential candidate drug target for ameliorating impaired glucose metabolism in diabetes.
Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research (CSIR), Hyderabad, India.
Vijay Pratap
VP
Singh
B Jyothi
BJ
Lakshmi
Shalu
S
Singh
Vanya
V
Shah
Sandeep
S
Goel
D Partha
DP
Sarathi
Satish
S
Kumar
D000818:Animals; D018797:Cell Cycle Proteins; D002460:Cell Line; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics; D006946:Hyperinsulinism / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000172:deficiency* / Q000378:metabolism
C493957:Cdkn1a protein, mouse; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D007328:Insulin; D009687:Nuclear Proteins; C508318:WDR13 protein, mouse