Ultrastructural Analyses of Acellular Glomerular Basement Membranes and Mesangial Matrix in a Spontaneously Diabetic Rhesus Monkey

Marion, Susan; Carlson, Edward C.

doi:10.1159/000146742

Cited by 10 publications

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“…At 300 days of age, MM in diabetic mice was concentrated in nodules comprised of ''nests'' of striated collagen fibrils and other basement membrane-like materials that, like their human diabetic equivalents (Carlson and Surerus, 1986), were located in centrolobular regions of glomeruli. Mouse MM nodules were not as compact as those seen in human diabetic end-stage glomerulopathy but closely resembled those reported in acellular diabetic rhesus monkey kidneys (Marion and Carlson, 1989).…”

Section: Discussionsupporting

confidence: 76%

“…The age-and diabetes-related increase in glomerular extracellular matrix identified by LM led us to initiate several electron microscopic experiments. Because we had previously extensively used the sequential detergent extraction method (Carlson et al, 1978) for generating isolated GBM and MM starting material for electron microscopic studies in normal Hinds, 1981, 1983;Carlson and Chatterjee, 1983;Carlson and Kenney, 1980a,b) and diabetics (Carlson and Surerus, 1986;Marion and Carlson, 1989), similar Fig. 2A with 3A).…”

Section: Discussionmentioning

confidence: 80%

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Ultrastructural and functional analyses of nephropathy in calmodulin‐induced diabetic transgenic mice

et al. 1997

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 80%

Ultrastructural and functional analyses of nephropathy in calmodulin‐induced diabetic transgenic mice

et al. 1997

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“…Because we had previously extensively used the sequential detergent extraction method (Carlson et al, 1978) for generating isolated GBM and MM starting material for electron microscopic studies in normal Hinds, 1981, 1983;Carlson and Chatterjee, 1983;Carlson and Kenney, 1980a,b) and diabetics (Carlson and Surerus, 1986;Marion and Carlson, 1989), similar Fig. 2A with 3A).…”

Section: Discussionmentioning

confidence: 80%

Ultrastructural and functional analyses of nephropathy in calmodulin-induced diabetic transgenic mice

et al. 1997

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Background Previous animal models of diabetic nephropathy have used diabetic animals for which the underlying defect was either uncertain or the diabetes was induced by potentially specific toxins. In this report, we describe the renal abnormalities in a transgenic mouse model that develops early‐onset diabetes due to overexpression of calmodulin in pancreatic beta cells. Methods Renal tissues were collected from normal and transgenic mice at 112, 182, and 300 days. These were prepared for light microscopic observation, stained with polyethylenimine (for anionic sites), or rendered acellular by detergent extraction prior to observation by transmission and scanning electron microscopy. Morphometric analysis of glomerular basement membrane thickness was carried out by the “orthogonal intercept” method. Twelve‐hour urine samples of fed and fasting mice were collected for urine volume and glucose and protein analyses. Blood glucose, blood urea nitrogen, serum insulin, and creatinine were determined in 60‐90‐day‐old and 255‐day‐old mice by established methods. Results Morphometric analyses revealed age‐related and transgene‐related increases in glomerular basement membrane thickness. A 22% increase in transgenic diabetics over controls was seen at 112 days of age that developed to increases of 43% and 37% at 182 and 300 days of age, respectively. Mesangial matrix area was also increased markedly in transgenic mice. Surprisingly, even in the oldest diabetic mice, there was no reduction in anionic sites. Moreover, despite an eightfold increase in urine volume, these mice did not become significantly proteinuric. Conclusions These results indicate that proteinuria of diabetes may be delayed or prevented by maintenance of a normal complement of glomerular basement membrane anionic sites. They also demonstrate that transgenic mice can provide a valuble model for discriminating between different aspects of diabetic nephropathy. Anat. Rec. 247:9–19 © 1997 Wiley‐Liss, Inc.

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“…We have previously shown in several species that at the level of LM, detergent treatment completely removed cellular components while glomerular ECM components, including various renal basement membranes, maintain their normal histoarchitectures Hinds, 1981, 1983;Carlson and Kenney, 1982;Carlson and Chatterjee, 1983;Carlson and Surerus, 1986;Marion and Carlson, 1989;Carlson et al, 1997). Likewise in the current study, whole acellular glomeruli from BB/DR, BB/DP h , and BB/ DP n animals at 1 year postonset of diabetes showed normal morphological features and were virtually indistinguishable with only minor increases in MM in BB/DP h kidneys.…”

Section: Light Microscopic Studiesmentioning

confidence: 99%

Significant glomerular basement membrane thickening in hyperglycemic and normoglycemic diabetic‐prone BB Wistar rats

et al. 2004

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The diabetic-prone BioBreeding Wistar rat (BB/DP) is an autoimmune model of insulindependent diabetes mellitus. Approximately 80 -90% of the animals are hyperglycemic (BB/ DP h ) by 90 -120 days of age while those that do not become diabetic in adolescence (BB/DP n ) remain normoglycemic for life. Likewise, rats in the diabetes-resistant (BB/DR) strain are normoglycemic. Although renal morphological studies have been carried out in this model, ultrastructural observations of age-and diabetes-related extracellular matrix (ECM) changes, including glomerular basement membrane (GBM) morphometry, are not available. Moreover, possible renal changes in the relatively uncommon BB/DP n control animals have not been reported. The current electron microscopic study was carried out to investigate temporal changes in detergent-treated acellular ECM in BB/DP h rats at 2 weeks, 3 months, 6 months, and 1 year postonset of moderate hyperglycemia. Age-matched BB/DR and BB/DP n control animals were also examined. Our data demonstrate age-and diabetes-related alterations in mesangial matrix distributions and GBM widths and show for the first time significant increases in GBM thickening in both hyperglycemic (BB/DP h ) and normoglycemic (BB/DP n ) rats when compared to age-matched BB/DR controls. Surprisingly, the rate of increase is greatest in BB/DP n animals. Although the pathogenesis of diabetic basement membrane disease is not completely understood, GBM thickening is widely regarded as a morphological consequence of hyperglycemia. However, data in the current investigation show that ECM alterations, including significantly increased GBM thickness, may occur in genetically diabetic animals in the absence of hyperglycemia. © 2004 Wiley-Liss, Inc. Key words: diabetes; glomerular basement membrane thickness; BB Wistar ratsThe BioBreeding Wistar rat (BB rat) is an autoimmune model of insulin-dependent diabetes mellitus (IDDM) discovered in 1974 in a colony of pathogen-free Wistar rats (Chappel and Chappel, 1983). Like human IDDM, the onset of clinical symptoms in diabetes-prone (BB/DP) BB rats appear during adolescence, generally between 60 and 120 days of age (Butler et al., 1983;Chappel and Chappel, 1983). These are characterized by rapid weight loss, polyuria, polydipsia, ketonuria, and finally death unless exogenous insulin is administered (Chappel and Chappel, 1983;Like and Rossini, 1984). The incidence of diabetes through 120 days of age is 60 -90% in most colonies and averaged 86% in a viral antibody-free NIH colony in Worcester, Massachusetts (Crisa et al., 1992). The diabetes exhibited by BB rats is not attributed to a single dominant or recessive gene, but the etiology seems to include a genetic component (Chappel and Chappel, 1983).

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Ultrastructural Analyses of Acellular Glomerular Basement Membranes and Mesangial Matrix in a Spontaneously Diabetic Rhesus Monkey

Cited by 10 publications

References 17 publications

Ultrastructural and functional analyses of nephropathy in calmodulin‐induced diabetic transgenic mice

Ultrastructural and functional analyses of nephropathy in calmodulin‐induced diabetic transgenic mice

Ultrastructural and functional analyses of nephropathy in calmodulin-induced diabetic transgenic mice

Significant glomerular basement membrane thickening in hyperglycemic and normoglycemic diabetic‐prone BB Wistar rats

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