A canine autosomal recessive model of collagen type III glomerulopathy

Rørtveit, Runa; Lingaas, Frode; Bønsdorff, Tina Bjørnlund; Eggertsdóttir, Anna V; Grøndahl, Ann Margaret; Thomassen, Ragnar; Fogo, Agnes B.; Jansen, J. H.

doi:10.1038/labinvest.2012.112

Cited by 11 publications

(32 citation statements)

References 33 publications

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“…Studying an affected mixed-breed dog strain, we have previously provided evidence for local mesangial cell collagen production and furthermore excluded the involvement of the Col3A1 gene in this dog strain. 22 While this particular gene might not be the ultimate source of this abnormality in dogs, there are various other genes involved in the posttransitional assembly of collagen fibrils. 12 As a response to injury, mesangial cells can acquire an activated phenotype with excessive production of various substances, including matrix proteins and growth factors 1 ; however, the marked mesangial cell production of collagen type III, characteristic for Col3GP, is not associated with other diseases, including mesangial cell injury.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, we have found evidence of collagen III synthesis by local mesangial cells in an affected mixed-breed dog strain. 22 A precise description of the composition of the pathological collagen could contribute to the understanding of the ongoing The pathogenesis of Col3GP is unknown. In dogs, an autosomal recessive inheritance pattern has been shown 22 ; however, the causative mutation has not been identified in humans or animals, and it is not known whether Col3GP is a primary renal disease or a systemic disorder.…”

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confidence: 99%

“…21 The clinical features in dogs are similar to those of affected children. 7 With one exception, 9 all described canine cases 10,11,21,22 developed clinical signs of chronic renal failure within a year of birth.…”

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confidence: 99%

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Glomerular Collagen V Codeposition and Hepatic Perisinusoidal Collagen III Accumulation in Canine Collagen Type III Glomerulopathy

et al. 2014

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Collagen type III glomerulopathy, also known as collagenofibrotic glomerulopathy, is a rare renal disease of unknown pathogenesis. The disease occurs in humans and animals and is characterized by massive glomerular accumulations of collagen type III. In the present study, we describe a Drever dog litter affected by an early onset variant of this glomerular disease, where 4 of 9 puppies developed renal failure within 50 days of age. Necropsy specimens of kidney from the 4 affected cases were studied by light microscopy, electron microscopy, and immunohistochemistry, and characteristic lesions compatible with a diagnosis of collagen type III glomerulopathy were found. In addition, 2 cases showed atypical epithelium in the collecting ducts of the medulla, so-called adenomatoid change. Immunohistochemistry of renal specimens from collagen type III glomerulopathy-affected dogs (n ¼ 10) originating from two different dog strains, the Drever dogs and a mixed-breed strain, demonstrated that the deposited glomerular collagen is composed of a mixture of collagen III and collagen V. The distribution of the collagen V corresponded to the localization of collagen III; however, differences in staining intensity showed that collagen type III is the dominating component. Immunohistochemistry for collagen III (n ¼ 9) and a transmission electron microscopic study (n ¼ 1) showed hepatic perisinusoidal collagen type III deposition in affected cases from both dog strains. This is the first report documenting glomerular accumulations of collagen type V and perisinusoidal liver collagen III deposition in canine collagen type III glomerulopathy.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Glomerular Collagen V Codeposition and Hepatic Perisinusoidal Collagen III Accumulation in Canine Collagen Type III Glomerulopathy

et al. 2014

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“…All glomeruli should be evaluated in a core biopsy and at least 50 glomeruli should be evaluated in wedge specimens. 4 The glomerular basement membrane (GBM) is best visualized in the peripheral capillary loops of the glomerular tufts and should be carefully examined for a normal smooth outer contour. Signs of GBM remodeling include spike-like projections, holes, double contours, irregular outer contours, or generalized thickening without the previously mentioned features.…”

Section: Box 1 Consensus Recommendations For the Pathologic Evaluatiomentioning

confidence: 99%

Pathologic Evaluation of Canine Renal Biopsies: Methods for Identifying Features that Differentiate Immune‐Mediated Glomerulonephritides from Other Categories of Glomerular Diseases

Cianciolo

Brown

Mohr

et al. 2013

Veterinary Internal Medicne

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Background: Human renal biopsies are routinely evaluated with light microscopy (LM) using a panel of histologic stains, transmission electron microscopy (TEM), and immunofluorescence (IF) microscopy to obtain a diagnosis. In contrast, the pathologic evaluation of glomerular disease in veterinary medicine has relied mostly on LM and was of limited utility. To address this problem, recently established veterinary renal diagnostic centers have adopted methods used in human nephropathology for evaluation of renal biopsies. Three broad categories of disease, which have the greatest implications for clinical management of proteinuric dogs, have been established and include amyloidosis, immune complex-mediated glomerulonephritis (ICGN), and non-ICGN.Objective: To demonstrate histopathologic, ultrastructural, and IF findings in renal biopsy specimens that experienced veterinary nephropathologists utilize to make accurate and clinically useful diagnoses in dogs with proteinuric glomerular disease and to provide guidelines for the proper evaluation of renal biopsies.Methods: Renal biopsy specimens were routinely examined by LM, IF, and TEM. Samples were reviewed by members of the World Small Animal Veterinary Association Renal Standardization Study Group to identify lesions that were diagnostic for, or suggestive of, the presence of immune complexes (IC) or amyloidosis in all modalities. Ten guidelines for renal biopsy evaluation were formulated.Results: Each method of investigation contributed important findings that were integrated to make an accurate final morphological diagnosis. The guidelines were validated by an independent group of veterinary pathologists.Conclusions and Clinical Importance: Routine evaluation of renal biopsies with LM, TEM, and IF is feasible and necessary for making accurate, morphologic diagnoses that can be used to guide clinical management of dogs with glomerular disease.

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“…62,63 Test matings indicated an autosomal mode of inheritance. As in humans, increased serum levels of the amino-terminal propeptide of type III procollagen (PIIINP) may be used as a marker of this defect.…”

Section: Abnormal Glomerular Deposition Collagen IIImentioning

confidence: 96%

Emerging perspectives on hereditary glomerulopathies in canines

Littman¹

2015

AGG

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Familial glomerulopathies have been described in more than two dozen dog breeds. These canine spontaneous cases of glomerular disease are good models for their human counterparts. The dogs present clinically with protein-losing nephropathy and variable signs of hypertension, thromboembolic events, edema/effusions/nephrotic syndrome, or eventually with signs of renal disease such as anorexia, vomiting, weight loss, and/or polyuria/polydipsia. Laboratory changes include proteinuria, hypoalbuminemia, hypercholesterolemia, and eventually azotemia, hyperphosphatemia, anemia, and isosthenuria. Renal biopsies examined with transmission electron microscopy, immunofluorescence, and thin section light microscopy may show ultrastructural glomerular basement membrane abnormalities, glomerulosclerosis, amyloidosis, non-amyloid fibrillary deposition, or breed-associated predispositions for immunecomplex glomerulonephritis. Genome-wide association studies and fine sequencing of candidate genes have led to the discovery of variant alleles associated with disease in some breeds; eg, 1) glomerular basement membrane ultrastructural abnormalities due to defective collagen type IV, caused by different premature stop codons in each of four breeds; ie, in COL4A5 in Samoyeds and Navasota mix breed dogs (X-linked), and in COL4A4 in English Cocker Spaniels and English Springer Spaniels (autosomal recessive); and 2) glomerulosclerosis-related podocytopathy with slit diaphragm protein anomalies of both nephrin and Neph3/filtrin due to nonsynonymous single nucleotide polymorphisms in conserved regions of their encoding genes, NPHS1 and KIRREL2, in Soft Coated Wheaten Terriers and Airedale Terriers, with a complex mode of inheritance. Age at onset and progression to end-stage renal disease vary depending on the model. Genetic counseling using DNA testing is available for several breeds but many more inherited canine models of glomerulopathy still need to be characterized. Dog breeds, with their long haplotypes and linkage disequilibrium, represent excellent models to study the underlying molecular basis for protein-losing nephropathy, glomerular function, genetic manipulations, possible environmental triggers, and treatments. Results of studies of genetic canine diseases will help dogs and other species, including man.

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A canine autosomal recessive model of collagen type III glomerulopathy

Cited by 11 publications

References 33 publications

Glomerular Collagen V Codeposition and Hepatic Perisinusoidal Collagen III Accumulation in Canine Collagen Type III Glomerulopathy

Glomerular Collagen V Codeposition and Hepatic Perisinusoidal Collagen III Accumulation in Canine Collagen Type III Glomerulopathy

Pathologic Evaluation of Canine Renal Biopsies: Methods for Identifying Features that Differentiate Immune‐Mediated Glomerulonephritides from Other Categories of Glomerular Diseases

Emerging perspectives on hereditary glomerulopathies in canines

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