Dataset Information

Glomerular Lesions in Proteinuric Miniature Schnauzer Dogs.

ABSTRACT: Miniature Schnauzer dogs are predisposed to idiopathic hypertriglyerceridemia, which increases risk for diseases such as pancreatitis and gallbladder mucocele. Recently, elevated triglyceride concentrations have been associated with proteinuria in this breed, although it is difficult to determine which abnormality is primary. Retrospective review of renal tissue from 27 proteinuric Miniature Schnauzers revealed that 20 dogs had ultrastructural evidence of osmophilic globules consistent with lipid in glomerular tufts. Seven of these dogs had lipid thromboemboli in glomerular capillary loops that distorted their shape and compressed circulating erythrocytes. Triglyceride concentrations were reported in 6 of these 7 dogs, and all were hypertriglyceridemic. In addition, glomerular lipidosis (defined as accumulation of foam cells within peripheral capillary loops) was identified in a single dog. The remaining 12 dogs had smaller amounts of lipid that could only be identified ultrastructurally. Neither signalment data nor clinicopathologic parameters (serum albumin, serum creatinine, urine protein-to-creatinine ratio, and blood pressure) differed among the various types of lipid lesions. During the time course of this study, all dogs diagnosed with glomerular lipid thromboemboli were Miniature Schnauzers, underscoring the importance of recognizing these clear spaces within capillary loops as lipid.

SUBMITTER: Furrow E

PROVIDER: S-EPMC5266673 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Glomerular Lesions in Proteinuric Miniature Schnauzer Dogs.

Furrow E E Lees G E GE Brown C A CA Cianciolo R E RE

Veterinary pathology 20161222 3

Miniature Schnauzer dogs are predisposed to idiopathic hypertriglyerceridemia, which increases risk for diseases such as pancreatitis and gallbladder mucocele. Recently, elevated triglyceride concentrations have been associated with proteinuria in this breed, although it is difficult to determine which abnormality is primary. Retrospective review of renal tissue from 27 proteinuric Miniature Schnauzers revealed that 20 dogs had ultrastructural evidence of osmophilic globules consistent with lipi ...[more]

PMID: 28005494

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Project description:BackgroundCharcot-Marie-Tooth (CMT) disease is the most common neuromuscular disorder in humans affecting 40 out of 100,000 individuals. In 2008, we described the clinical, electrophysiological and pathological findings of a demyelinating motor and sensory neuropathy in Miniature Schnauzer dogs, with a suspected autosomal recessive mode of inheritance based on pedigree analysis. The discovery of additional cases has followed this work and led to a genome-wide association mapping approach to search for the underlying genetic cause of the disease.MethodsFor genome wide association screening, genomic DNA samples from affected and unaffected dogs were genotyped using the Illumina CanineHD SNP genotyping array. SBF2 and its variant were sequenced using primers and PCRs. RNA was extracted from muscle of an unaffected and an affected dog and RT-PCR performed. Immunohistochemistry for myelin basic protein was performed on peripheral nerve section specimens.ResultsThe genome-wide association study gave an indicative signal on canine chromosome 21. Although the signal was not of genome-wide significance due to the small number of cases, the SBF2 (also known as MTMR13) gene within the region of shared case homozygosity was a strong positional candidate, as 22 genetic variants in the gene have been associated with demyelinating forms of Charcot-Marie-Tooth disease in humans. Sequencing of SBF2 in cases revealed a splice donor site genetic variant, resulting in cryptic splicing and predicted early termination of the protein based on RNA sequencing results.ConclusionsThis study reports the first genetic variant in Miniature Schnauzer dogs responsible for the occurrence of a demyelinating peripheral neuropathy with abnormally folded myelin. This discovery establishes a genotype/phenotype correlation in affected Miniature Schnauzers that can be used for the diagnosis of these dogs. It further supports the dog as a natural model of a human disease; in this instance, Charcot-Marie-Tooth disease. It opens avenues to search the biological mechanisms responsible for the disease and to test new therapies in a non-rodent large animal model. In particular, recent gene editing methods that led to the restoration of dystrophin expression in a canine model of muscular dystrophy could be applied to other canine models such as this before translation to humans.

Project description:Identification of glomerular lesions and structures is a key point for pathological diagnosis, treatment instructions, and prognosis evaluation in kidney diseases. These time-consuming tasks require a more accurate and reproducible quantitative analysis method. We established derivation and validation cohorts composed of 400 Chinese patients with immunoglobulin A nephropathy (IgAN) retrospectively. Deep convolutional neural networks and biomedical image processing algorithms were implemented to locate glomeruli, identify glomerular lesions (global and segmental glomerular sclerosis, crescent, and none of the above), identify and quantify different intrinsic glomerular cells, and assess a network-based mesangial hypercellularity score in periodic acid-Schiff (PAS)-stained slides. Our framework achieved 93.1% average precision and 94.9% average recall for location of glomeruli, and a total Cohen's kappa of 0.912 [95% confidence interval (CI), 0.892-0.932] for glomerular lesion classification. The evaluation of global, segmental glomerular sclerosis, and crescents achieved Cohen's kappa values of 1.0, 0.776, 0.861, and 95% CI of (1.0, 1.0), (0.727, 0.825), (0.824, 0.898), respectively. The well-designed neural network can identify three kinds of intrinsic glomerular cells with 92.2% accuracy, surpassing the about 5-11% average accuracy of junior pathologists. Statistical interpretation shows that there was a significant difference (P value < 0.0001) between this analytic renal pathology system (ARPS) and four junior pathologists for identifying mesangial and endothelial cells, while that for podocytes was similar, with P value = 0.0602. In addition, this study indicated that the ratio of mesangial cells, endothelial cells, and podocytes within glomeruli from IgAN was 0.41:0.36:0.23, and the performance of mesangial score assessment reached a Cohen's kappa of 0.42 and 95% CI (0.18, 0.69). The proposed computer-aided diagnosis system has feasibility for quantitative analysis and auxiliary recognition of glomerular pathological features. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Dataset Information

Glomerular Lesions in Proteinuric Miniature Schnauzer Dogs.

Publications

Glomerular Lesions in Proteinuric Miniature Schnauzer Dogs.

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