Genetic renal disease

Saborío, Pablo; Scheinman, Jon I.

doi:10.1097/00008480-199804000-00011

Cited by 15 publications

(10 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…No indications of glomerular, renal vascular, or tubulointerstitial injury were found. Thus, fibrillin-1 underexpression in mice does not seem to lead to defects in renal function, despite some reports of glomerular disease in patients with Marfan syndrome [12,22,24]. Sbar et al [24] described four Marfan patients with microhematuria and proteinuria.…”

Section: Discussionmentioning

confidence: 99%

“…Regarding its localization surrounding the glomerular capillaries, it seems likely that fibrillin-1 could contribute to the elastic strength and anchorage of the glomerular capillary tuft, a structure that is exposed to a high hydrostatic pressure to maintain a high ultrafiltration rate [28]. Several reports of different types of renal disease in Marfan patients have appeared [5,12,22,24,25], but it remains unknown whether these associations were coincidental or due to a systematic renal defect caused by the fibrillin-1 mutation. Studies have reported two models of fibrillin-1 gene-mutated mice [17,18].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Characterization of the renal phenotype in a mouse model of Marfan syndrome

et al. 2004

View full text Add to dashboard Cite

The microfibrillar protein fibrillin-1 is expressed abundantly in the vasculature and the glomerulus of the kidney. Mutations in the fibrillin-1 gene lead to Marfan syndrome. The most common complication of this disease is aortic dilatation due to elastic deficiencies of the vascular wall. Several case reports describe glomerular disease in patients with Marfan syndrome, and fibrillin-1 has been implicated in nephrogenesis. To study the role of fibrillin-1 in renal development and function, we characterized the renal phenotype of fibrillin-1-underexpressing mice. Kidney histology was evaluated by means of morphometry and stereology. Relative kidney weights, daily urine excretion, urinary albumin excretion, serum and urinary creatinine, as well as serum urea were not different than wild-type mice. Glomerular number and renal capillarization were normal. The size of the renal filtration surface was comparable in wild-type and fibrillin-1-underexpressing mice. There was no indication for glomerular, renal vascular, or tubulointerstitial injury. However, glomerular volume and mesangial area were reduced. No changes in glomerular cell numbers were detected, but the cellular volume of mesangial cells was significantly lower in glomeruli of fibrillin-1-underexpressing mice. Thus, despite the high abundance of fibrillin-1 in glomeruli of wild-type animals, underexpression of fibrillin-1 did not lead to functional deficiencies of the glomerulus. Alterations in renal histology were only subtle with a reduced glomerular volume and mesangial area likely due to a reduced mesangial cell volume.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of the renal phenotype in a mouse model of Marfan syndrome

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Among these are glomerular basement membrane defects as well as tubular and interstitial alterations. Once chronic renal insufficiency is established, it tends to progress to end-stage kidney failure, which is characterized by progressive glomerulosclerosis irrespective of the initiating nephropathy (25). Few appropriate animal models are available to date for the examination of genes involved in chronic kidney diseases (1,4,13,30,32).…”

mentioning

confidence: 99%

Screening for increased plasma urea levels in a large-scale ENU mouse mutagenesis project reveals kidney disease models

Aigner¹,

Rathkolb²,

Herbach³

et al. 2007

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Kidney diseases lead to the failure of urinary excretion of metabolism products. In the Munich ethylnitrosourea (ENU) mouse mutagenesis project, which is done on a C3H inbred genetic background, blood samples of more than 15,000 G1 offspring and 500 G3 pedigrees were screened for alterations in clinical-chemical parameters. We identified 44 animals consistently exhibiting increased plasma urea concentrations. Transmission analysis of the altered phenotype of 23 mice to subsequent generations led to the establishment of five mutant lines. Both sexes were affected in these lines. Urinary urea levels were decreased in the mutants. In addition, most mutants showed increased plasma and decreased urinary creatinine levels. Pathological investigation of kidneys from the five mutant lines revealed a broad spectrum of alterations, ranging from no macroscopic and light microscopic kidney alterations to decreased kidney weight-to-body weight ratio, dilation of the renal pelvis, and severe glomerular lesions. Thus screening for elevated plasma urea levels in a large-scale ENU mouse mutagenesis project resulted in the successful establishment of mouse strains which are valuable tools for molecular studies of mechanisms involved in urea excretion or which represent interesting models for kidney diseases.

show abstract

“…The function of fibrillin-1 in the glomerular mesangium, however, is not known. Several case reports describing different types of glomerular disease in patients with Marfan syndrome have been published (1,11,17,18,22), but there is no evidence that this is more than a chance association. No systematic study on renal sequelae of Marfan syndrome has been performed so far.…”

mentioning

confidence: 99%

Role of fibrillin-1 in hypertensive and diabetic glomerular disease

Hartner¹,

Schaefer²,

Porst³

et al. 2006

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

The microfibrillar protein fibrillin-1 is a component of the mesangial matrix. Defects in fibrillin-1 predisposes individuals to vascular damage in Marfan syndrome, but the role of fibrillin-1 in kidney disease is unknown. We hypothesized that fibrillin-1 is involved in hypertensive or diabetic glomerular disease. DOCA-salt hypertension or streptozotocin (STZ) diabetes led to a significant increase in glomerular fibrillin-1 deposition. To test the functional role of fibrillin-1, DOCA hypertension and STZ diabetes were induced in mice homozygous for a mutation leading to a fivefold lower expression of fibrillin-1 (mgR/mgR). Untreated male mgR/mgR mice usually die from aortic dissection during the first 4 mo of life. All DOCA-treated mgR/mgR mice died within 2 wk after onset of DOCA treatment. DOCA-treated heterozygous (mgR/+) and their wild-type littermates displayed similar blood pressure levels, but albuminuria was significantly lower in mgR/+ than in wild-type mice after DOCA treatment. Similarly, STZ diabetic mgR/mgR and mgR/+ developed lower albuminuria than wild-type mice despite higher blood glucose levels in mgR/mgR and mgR/+ compared with wild-type mice. Blood pressure, blood glucose, and albuminuria did not differ among untreated mgR/mgR, mgR/+, and wild-type mice, respectively. In diabetic mgR/+ and mgR/mgR, but not in wild-type mice, an induction of glomerular decorin expression was observed. Thus underexpression of fibrillin-1 predisposes individuals to lethal aortic dissection in the presence of hypertension. On the other hand, albuminuria as a parameter of microvascular damage in hypertension and diabetes was ameliorated in fibrillin-1-underexpressing mice, possibly due to a compensatory upregulation of decorin. We conclude that fibrillin-1 may contribute to glomerular damage in hypertensive and diabetic kidney disease.

show abstract

Genetic renal disease

Cited by 15 publications

References 0 publications

Characterization of the renal phenotype in a mouse model of Marfan syndrome

Characterization of the renal phenotype in a mouse model of Marfan syndrome

Screening for increased plasma urea levels in a large-scale ENU mouse mutagenesis project reveals kidney disease models

Role of fibrillin-1 in hypertensive and diabetic glomerular disease

Contact Info

Product

Resources

About