Role of zinc finger transcription factor zfp69 in body fat storage and diabetes susceptibility of mice.
Type 2 diabetes is a polygenic disease resulting from a combination of different disease alleles reflecting obesity, insulin resistance, and hyperglycemia. Using a positional cloning strategy with different inbred strains of mice, we mapped a disease locus for obesity-associated diabetes on chromosome 4. We analyzed all genes in this region and identified distinct differences in the expression levels of the transcription factor Zfp69. The expression of this gene mediated diabetes progression in a leptin-deficient congenic mouse line. The animals developed a disease pattern of hyperglycemia, reduced gonadal fat mass, and increased plasma and liver triglycerides, resembling a potential defect in triglyceride storage . In order to elucidate the impact of the human ortholog of Zfp69 in the development of type 2 diabetes, we tested its mRNA expression in human white adipose tissue. Consistent with the mouse data, mRNA-expression was significantly higher in diabetic subjects than in unaffected controls.
Scherneck
Stephan
S
German Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany. scherneck@dife.de
Vogel
Heike
H
Nestler
Matthias
M
Kluge
Reinhart
R
Schürmann
Annette
A
Joost
Hans-Georg
HG
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D051379:Mice; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016335:Zinc Fingers / Q000235:genetics / Q000502:physiology
D014157:Transcription Factors; C544163:Zfp69 protein, mouse