International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


POSTER 77 - FUNCTIONAL ANALYSIS OF THE DEVELOPMENT OF DIABETIC NEPHROPATHY IN MOUSE MODELS OF TYPE II DIABETES

Bentley E
Diabetes, QTL and Modifier Loci Group, MRC Harwell, Oxfordshire, UK

Co-Authors: Paul C L, Quarterman J M, Goldsworthy M, Cox R D
Institutions: Diabetes, QTL and Modifier Loci Group, MRC Harwell, Oxfordshire, UK

In the UK diabetes affects more than 1.4 million people (3% total population) plus at least 1 million undiagnosed. Type II diabetes affects approximately 85% of Caucasian diabetes patients and is higher in other populations. Diabetes causes substantial morbidity and mortality mainly through cardiovascular disease, retinopathy, neuropathy, kidney disease and through limb amputation as a result of peripheral vascular disease.

Diabetic nephropathy is one of the most serious complications associated with this disease and is the number one cause of end-stage renal disease necessitaing dialysis or transplantation.

As part of the EURAGEDIC* consortium (EU FP5), which aims to identify genes that could predetermine whether diabetes sufferers will develop diabetic nephropathy, we have been studying a number of mouse lines for diabetic kidney disease. Our aim is to identify genes and pathways involved in the development of diabetic nephropathy in mouse models of type II diabetes. We have phenotyped seven ENU induced lines for plasma glucose and insulin levels, urine analysis and histological measurements of mesangial matrix accumulation. In addition, we have chosen a known type II diabetes mouse model, Lepr db/db, with which we are performing expression profiling experiments. We will present data on the phenotypic characterisation of a number of the mouse models derived from ENU screens and microarray data obtained over a time-course during the development of diabetic nephropathy in Lepr db/db in comparison to wild-type misty controls.

*European Rational Approach for the Genetics of Diabetic Complications

(QLG2-CT-2001-01669)


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