Gene expression profile in diabetic KK/Ta mice.

Background: To identify susceptibility genes for diabetic nephropathy, GeneChip Expression Analysis was employed to survey the gene expression profile of diabetic KK/Ta mouse kidneys.

Methods: Kidneys from three KK/Ta and two BALB/c mice at 20 weeks of age were dissected. Total RNA was extracted and labeled for hybridizing to the Affymetrix Murine Genome U74Av2 array. The gene expression profile was compared between KK/Ta and BALB/c mice using GeneChip expression analysis software. Competitive reverse transcription-polymerase chain reaction (RT-PCR) was used to confirm the results of GeneChip for a selected number of genes.

Results: Out of 12,490 probe pairs present on GeneChip, 98 known genes and 31 expressed sequence tags (ESTs) were found to be differentially expressed between KK/Ta and BALB/c kidneys. Twenty-one known genes and seven ESTs that increased in expression and 77 known genes and 24 ESTs that decreased in KK/Ta kidneys were identified. These genes are related to renal function, extracellular matrix expansion and degradation, signal transduction, transcription regulation, ion transport, glucose and lipid metabolism, and protein synthesis and degradation. In the vicinity of UA-1 (quantitative trait locus for the development of albuminuria in KK/Ta mice), candidate genes that showed differential expression were identified, including the Sdc4 gene for syndecan-4, Ahcy gene for S-adenosylhomocysteine hydrolase, Sstr4 gene for somatostatin receptor 4, and MafB gene for Kreisler leucine zipper protein.

Conclusion: The gene expression profile in KK/Ta kidneys is different from that in age-matched BALB/c kidneys. Altered gene expressions in the vicinity of UA-1 may be responsible for the development of albuminuria in diabetic KK/Ta mice.