Using the ZDF rat for diabetes studies

Charles River supplied RenaSci with Zucker Diabetic Fatty (ZDF-Leprfa/Crl) rats that contained a mutation in the fa/fa gene

RenaSci is a contract research organisation based in Nottingham, UK, specialising in diabetes, obesity studies, CNS techniques and drug abuse testing. During November of 2013, Charles River supplied RenaSci with Zucker Diabetic Fatty (ZDF-Leprfa/Crl) rats that contained a mutation in the fa/fa gene.

ZDF rats are widely used to model type 2 diabetes and other aspects of the metabolic syndrome. The colony of ZDF rats supplied to RenaSci was established at the Charles River site in France, and was rederived mainly from the foundation colony at Charles River Wilmington, Massachusetts site. The diabetic phenotype of these rats was characterised during this collaboration.

In the study, twenty male ZDF fa/fa rats and 10 appropriate control rats (+/+ or +/fa) were supplied to RenaSci at six weeks of age. The animals were maintained on Purina 5008 diet. A variety of different parameters was measured, including body weight, food and water intake, glycaemic control and renal function.

The ZDF fa/fa rats displayed obesity, hyperphagia and polydipsia as expected when compared with the lean control group. Fasting plasma glucose levels markedly increased with age and blood HbA1c levels were increased (week 19) confirming the development of diabetes. An oral glucose tolerance test, performed during week 12, demonstrated impaired glucose tolerance and reduced insulin secretion following a glucose challenge (indicating the start of pancreatic failure).

Urinary volume and glucose excretion (week 16) was markedly increased, which is consistent with diabetes. Albuminuria was observed demonstrating diabetes-induced renal damage. Importantly, the ZDF fa/fa rats displayed hyperfiltration (increased glomerular filtration) at 20 weeks, a measure widely taken to be a precursor marker of progressive diabetic nephropathy. These findings confirmed that this colony of ZDF rats can be used to model type 2 diabetes and associated renal damage.

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