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Distinct genetic regulation of progression of diabetes and renal disease in the Goto-Kakizaki rat.

Authors: Nobrega, MA  Woods, LC  Fleming, S  Jacob, HJ 
Citation: Nobrega MA, etal., Physiol Genomics. 2009 Sep 9;39(1):38-46. Epub 2009 Jul 7.
Pubmed: (View Article at PubMed) PMID:19584172
DOI: Full-text: DOI:10.1152/physiolgenomics.90389.2008

Goto-Kakizaki (GK) rats develop early-onset type 2 diabetes (T2D) symptoms, with signs of diabetic nephropathy becoming apparent with aging. To determine whether T2D and renal disease share similar genetic architecture, we ran a quantitative trait locus (QTL) analysis in the F2 progeny of a GK x Brown Norway (BN) rat cross. Further, to determine whether genetic components change over time, we ran the QTL analysis on phenotypes collected longitudinally, at 3, 6, 9 and 12 mo, from the same animals. We confirmed three chromosomal regions that are linked to early diabetes phenotypes (chromosomes 1, 5, and 10) and a single region involved in the late progression of the disorder (chromosome 4). A single region was identified for the onset of the renal phenotype proteinuria (chromosome 5). This region overlaps the diabetic QTL, although it is not certain whether similar genes are involved in both phenotypes. A second QTL linked to the progression of the renal phenotype was found on chromosome 7. Linkage for triglyceride and cholesterol levels were also identified (chromosomes 7 and 8, respectively). These results demonstrate that, in general, different genetic components control diabetic and renal phenotypes in a diabetic nephropathy model. Furthermore, these results demonstrate that, over time, different genetic components are involved in progression of disease from those that were involved in disease onset. This observation would suggest that clinical studies collecting participants over a wide age distribution may be diluting genetic effects and reducing power to detect true effects.


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CRRD Object Information
CRRD ID: 2316856
Created: 2010-03-01
Species: All species
Last Modified: 2010-03-01
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.