Sequence of Changes in KK Mouse Nephropathy

Wehner, H.

doi:10.1007/978-1-4684-5616-5_18

Cited by 6 publications

(3 citation statements)

References 6 publications

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“…The KK strain has previously been proposed to represent a model of diabetic nephropathy (17,(41)(42)(43). The present finding of moderate albuminuria in nondiabetic KK/HlJ mice (Fig.…”

Section: Diabetes Vol 54 September 2005supporting

confidence: 60%

Characterization of Susceptibility of Inbred Mouse Strains to Diabetic Nephropathy

et al. 2005

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Differential susceptibility to diabetic nephropathy has been observed in humans, but it has not been well defined in inbred strains of mice. The present studies characterized the severity of diabetic nephropathy in six inbred mouse strains including C57BL/6J, DBA/2J, FVB/NJ, MRL/MpJ, A/J, and KK/HlJ mice. Diabetes mellitus was induced using low-dose streptozotocin injection. Progression of renal injury was evaluated by serial measurements of urinary albumin excretion, glomerular filtration rate (GFR), and terminal assessment of renal morphology over 25 weeks. Despite comparable levels of hyperglycemia, urinary albumin excretion and renal histopathological changes were dramatically different among strains. DBA/2J and KK/HlJ mice developed significantly more albuminuria than C57BL/6J, MRL/MpJ, and A/J mice. Severe glomerular mesangial expansion, nodular glomerulosclerosis, and arteriolar hyalinosis were observed in diabetic DBA/2J and KK/HlJ mice. Glomerular hyperfiltration was observed in all diabetic strains studied except A/J. The significant decline in GFR was not evident over the 25-week period of study, but diabetic DBA/2J mice exhibited a tendency for GFR to decline. Taken together, these results indicate that differential susceptibility to diabetic nephropathy exists in inbred mice. DBA/2J and KK/HlJ mice are more prone to diabetic nephropathy, whereas the most widely used C57BL/6J mice are relatively resistant to development of diabetic nephropathy. Diabetes 54:2628 -2637, 2005

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“…The KK strain has previously been proposed to represent a model of diabetic nephropathy (17,(41)(42)(43). The present finding of moderate albuminuria in nondiabetic KK/HlJ mice (Fig.…”

Section: Diabetes Vol 54 September 2005supporting

confidence: 60%

Characterization of Susceptibility of Inbred Mouse Strains to Diabetic Nephropathy

et al. 2005

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“…Immunohistologic studies show an intense, specific fluorescence for c -globulin in the enlarged mesangium and nodules and along the capillary wall. Albumin excretion in diabetic KK/Ta mice is demonstrably increased several weeks after establishment of hyperglycemia and, as in the human disease, presumably represents intact leaking nephrons without overt reduction in the single nephron glomerular filtration rate (GFR) [5][6][7]. Therefore, KK/Ta mice may serve as a suitable model for the study of type 2 diabetes and diabetic nephropathy in humans.…”

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confidence: 99%

Gene expression profile in diabetic KK/Ta mice

Fan

Shike

Shigihara

et al. 2003

Kidney International

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“…Kidneys are generally enlarged in this mouse strain, and structural glomerular changes (e.g., diffuse glomerulosclerosis, GBM thickening) occur without evidence of tubulointerstitial disease (40). Glomerular lesions of the KK mice are characterized by diffuse and nodular mesangial sclerosis without evidence of tubular disease (45). The lack of reliable mouse models prompted the National Institute of Diabetes and Digestive and Kidney Diseases to fund a consortium for the development and phenotyping of new diabetic mouse models that would resemble closely human DNP.…”

Section: Functional Genomic Studies Of Kidneys In Existing Rodent Modmentioning

confidence: 92%

Genomic Strategies for Diabetic Nephropathy

Suszták¹,

Sharma

Schiffer³

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Insight into the molecular mechanisms that underlie the origin and progression of diabetic nephropathy remains limited in part because conventional research tools have restricted investigators to focus on single genes or isolated pathways. Microarray technologies provide opportunities for evaluating genetic factors and environmental effects at a genomic scale during the pathogenesis of diabetic nephropathy. Despite the enormous power of the microarray technology, there are several pitfalls that need to be considered. This article discusses conceptual, practical, statistical, and logistical considerations for the use of microarrays in studies of experimental and human diabetic renal disease. New knowledge in this field will facilitate new approaches for molecular diagnosis and drug discovery.Diabetes is the most common metabolic disorder with an estimated worldwide prevalence between 1 and 5%. One of the most severe complications of diabetes is the development of diabetic nephropathy (DNP). Diabetic renal disease is the single most common cause of ESRD in the United States, accounting for 43% of new cases (1,2). Furthermore, diabetic ESRD is associated with a poor life expectancy.Clinical studies have identified risk factors that correlate with the development of ESRD in diabetes. The presence of microalbuminuria, hypertension, and poor glycemic control are the most important risk factors (3). It is clear, however, that poor glycemic control alone is not sufficient for the development of this complication. Long-term observational studies show that a maximum of 35% of patients develop nephropathy, irrespective of glycemic control (4). This is in contrast to retinopathy, for which the prevalence continues to rise with the duration of diabetes. Family studies showed that among patients with type 1 diabetes, when one sibling develops nephropathy, the other one has a fourfold increased risk of nephropathy compared with the sibling of a patient without nephropathy (5). These observations have clearly established the importance of genetic risk factors in the development of DNP.

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Sequence of Changes in KK Mouse Nephropathy

Cited by 6 publications

References 6 publications

Characterization of Susceptibility of Inbred Mouse Strains to Diabetic Nephropathy

Characterization of Susceptibility of Inbred Mouse Strains to Diabetic Nephropathy

Gene expression profile in diabetic KK/Ta mice

Genomic Strategies for Diabetic Nephropathy

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