| 1. |
- Ahlgren, Kerstin. M, et al.
(författare)
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Diabetes mellitus in dog - : No evidence for a type-1-like phenotype
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Aims/hypothesis Diabetes mellitus (DM) is one of the most common endocrine disorders in dogs, and is commonly proposed to be of autoimmune origin. Although the clinical symptoms of human type 1 diabetes (T1D) and canine DM are similar, the aetiologies may differ. The aim of this study was to investigate if autoimmune aetiology resembling human T1D is as prevalent in dogs as previously reported. Methods Sera from 121 diabetic dogs representing 38 different breeds were tested for islet cell antibodies (ICA) and GAD65 autoantibodies (GADA) and compared with sera from 133 healthy dogs from 40 breeds. ICA was detected by indirect immunofluorescence using both canine and human frozen sections. GADA was detected by in vitro transcription and translation (ITT) of human and canine GAD65, followed by immunoprecipitation. Results None of the canine sera analyzed tested positive for ICA on sections of frozen canine or human ICA pancreas. However, serum from one diabetic dog was weakly positive in the canine GADA assay and serum from one healthy dog was weakly positive in the human GADA assay. Conclusions/interpretations Based on sera from 121 diabetic dogs from 38 different breeds were tested for humoral autoreactivity using four different assays, contrary to previous observations, we find no support for an autoimmune aetiology in canine diabetes.
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| 2. |
- Ahlgren, Kerstin M, et al.
(författare)
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Lack of evidence for a role of islet autoimmunity in the aetiology of canine diabetes mellitus
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8, s. e105473-
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS:Diabetes mellitus is one of the most common endocrine disorders in dogs and is commonly proposed to be of autoimmune origin. Although the clinical presentation of human type 1 diabetes (T1D) and canine diabetes are similar, the aetiologies may differ. The aim of this study was to investigate if autoimmune aetiology resembling human T1D is as prevalent in dogs as previously reported.METHODS:Sera from 121 diabetic dogs representing 40 different breeds were tested for islet cell antibodies (ICA) and GAD65 autoantibodies (GADA) and compared with sera from 133 healthy dogs. ICA was detected by indirect immunofluorescence using both canine and human frozen sections. GADA was detected by in vitro transcription and translation (ITT) of human and canine GAD65, followed by immune precipitation. Sections of pancreata from five diabetic dogs and two control dogs were examined histopathologically including immunostaining for insulin, glucagon, somatostatin and pancreas polypeptide.RESULTS:None of the canine sera analysed tested positive for ICA on sections of frozen canine or human ICA pancreas. However, serum from one diabetic dog was weakly positive in the canine GADA assay and serum from one healthy dog was weakly positive in the human GADA assay. Histopathology showed marked degenerative changes in endocrine islets, including vacuolisation and variable loss of immune-staining for insulin. No sign of inflammation was noted.CONCLUSIONS/INTERPRETATIONS:Contrary to previous observations, based on results from tests for humoral autoreactivity towards islet proteins using four different assays, and histopathological examinations, we do not find any support for an islet autoimmune aetiology in canine diabetes mellitus.
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| 3. |
- Ahlgren, Kerstin, M., et al.
(författare)
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Type I Interferon signature in Nova Scotia duck tolling retriever dogs with steroid responsive meningitis-arteritis
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objective: Dogs of the breed Nova Scotia duck tolling retriever (NSDTR) are prone to develop a disease complex in some aspects resembling human systemic lupus erythematosus (SLE). Peripheral blood mononuclear cells (PBMCs) from human SLE patients have an increased mRNA expression type I interferon (IFN) regulated genes. However, it is unknown whether diseased dogs also display the typical type I IFN signature. Methods: To test canine sera for their capacity to induce type I IFN response Mardin-Darby canine kidney (MDCK) cells were cultured with sera from healthy dogs (n=25), immune-mediated rheumatic disease (IMRD) dogs with anti-nuclear antibodies (ANA+) (n=30) or dogs with steroid responsive meningitis-arteritis (SRMA) (n=25). mRNA expression of the genes MX1, IFIT1 and CXCL10 was measured by quantitative Real Time PCR. Results: A highly significant (p=0.0009) increase in mRNA expression of the type I IFN responsive gene MX1 was detected in cells stimulated by sera from dogs with SRMA, but not from IMRD ANA+ dogs. Expression of IFIT1 was twice as high in cells stimulated by sera from dogs with SRMA compared to both healthy dogs and ANA+ dogs. The mean expression of CXCL10 was nearly ten times higher in cells stimulated by sera from SRMA dogs than by ANA+ dogs and four times higher compared to cells stimulated by control dogs. Conclusion: Presence of type I IFN in sera from diseased NSDTR dogs was found in this study. This implies that this canine model can be used for identification of pathways of importance for autoimmune disorders in humans and for testing of novel therapeutic approaches. Our results can also be a step on the way towards personalized drugs in these dogs.
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| 4. |
- Ardesjö-Lundgren, Brita, et al.
(författare)
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Comparison of cellular location and expression of Plakophilin-2 in epidermal cells from nonlesional atopic skin and healthy skin in German shepherd dogs
- 2017
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Ingår i: Veterinary dermatology (Print). - : Wiley. - 0959-4493 .- 1365-3164. ; 28:4, s. 377-e88
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundCanine atopic dermatitis (CAD) is an inflammatory and pruritic allergic skin disease caused by interactions between genetic and environmental factors. Previously, a genome‐wide significant risk locus on canine chromosome 27 for CAD was identified in German shepherd dogs (GSDs) and Plakophilin‐2 (PKP2) was defined as the top candidate gene. PKP2 constitutes a crucial component of desmosomes and also is important in signalling, metabolic and transcriptional activities.ObjectivesThe main objective was to evaluate the role of PKP2 in CAD by investigating PKP2 expression and desmosome structure in nonlesional skin from CAD‐affected (carrying the top GWAS SNP risk allele) and healthy GSDs. We also aimed at defining the cell types in the skin that express PKP2 and its intracellular location.Animals/MethodsSkin biopsies were collected from nine CAD‐affected and five control GSDs. The biopsies were frozen for immunofluorescence and fixed for electron microscopy immunolabelling and morphology.ResultsWe observed the novel finding of PKP2 expression in dendritic cells and T cells in dog skin. Moreover, we detected that PKP2 was more evenly expressed within keratinocytes compared to its desmosomal binding‐partner plakoglobin. PKP2 protein was located in the nucleus and on keratin filaments attached to desmosomes. No difference in PKP2 abundance between CAD cases and controls was observed.ConclusionPlakophilin‐2 protein in dog skin is expressed in both epithelial and immune cells; based on its subcellular location its functional role is implicated in both nuclear and structural processes.
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| 5. |
- Brander, Gustaf, et al.
(författare)
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Multiple Genetic Loci Associated with Pug Dog Thoracolumbar Myelopathy
- 2023
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Ingår i: Genes. - : MDPI. - 2073-4425 .- 2073-4425. ; 14:2
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Tidskriftsartikel (refereegranskat)abstract
- Pug dogs with thoracolumbar myelopathy (PDM) present with a specific clinical phenotype that includes progressive pelvic limb ataxia and paresis, commonly accompanied by incontinence. Vertebral column malformations and lesions, excessive scar tissue of the meninges, and central nervous system inflammation have been described. PDM has a late onset and affects more male than female dogs. The breed-specific presentation of the disorder suggests that genetic risk factors are involved in the disease development. To perform a genome-wide search for PDM-associated loci, we applied a Bayesian model adapted for mapping complex traits (BayesR) and a cross-population extended haplotype homozygosity test (XP-EHH) in 51 affected and 38 control pugs. Nineteen associated loci (harboring 67 genes in total, including 34 potential candidate genes) and three candidate regions under selection (with four genes within or next to the signal) were identified. The multiple candidate genes identified have implicated functions in bone homeostasis, fibrotic scar tissue, inflammatory responses, or the formation, regulation, and differentiation of cartilage, suggesting the potential relevance of these processes to the pathogenesis of PDM.
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| 6. |
- Eriksson, D, et al.
(författare)
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Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
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| 7. |
- Fall, Tove, 1979-, et al.
(författare)
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Diabetes Mellitus in Elkhounds Is Associated with Diestrus and Pregnancy
- 2010
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Ingår i: Journal of Veterinary Internal Medicine. - : Wiley. - 0891-6640 .- 1939-1676. ; 24:6, s. 1322-1328
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Tidskriftsartikel (refereegranskat)abstract
- Background: Female Elkhounds are shown to be at increased risk for diabetes mellitus, and occurrence of diabetes during pregnancy has been described in several cases. Hypothesis: Onset of diabetes mellitus in Elkhounds is associated with diestrus. Animals: Sixty-three Elkhounds with diabetes mellitus and 26 healthy controls. Methods: Medical records from 63 Elkhounds with diabetes were reviewed and owners were contacted for follow-up information. Blood samples from the day of diagnosis were available for 26 dogs. Glucose, fructosamine, C-peptide, growth hormone (GH), insulin-like growth factor-1, progesterone, and glutamate decarboxylase isoform 65-autoantibodies were analyzed and compared with 26 healthy dogs. Logistic models were used to evaluate the association of clinical variables with the probability of diabetes and with permanent diabetes mellitus after ovariohysterectomy (OHE). Results: All dogs in the study were intact females and 7 dogs (11%) were pregnant at diagnosis. The 1st clinical signs of diabetes mellitus occurred at a median of 30 days (interquartile range [IQR], 3-45) after estrus, and diagnosis was made at a median of 46 days (IQR, 27-62) after estrus. Diabetes was associated with higher concentrations of GH and lower concentrations of progesterone compared with controls matched for time after estrus. Forty-six percent of dogs that underwent OHE recovered from diabetes with a lower probability of remission in dogs with higher glucose concentrations (odds ratio [OR], 1.2; P = .03) at diagnosis and longer time (weeks) from diagnosis to surgery (OR, 1.5; P = .05). Conclusions: Diabetes mellitus in Elkhounds develops mainly during diestrus and pregnancy. Immediate OHE improves the prognosis for remission of diabetes.
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| 8. |
- Owczarek-Lipska, Marta, et al.
(författare)
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Two Loci on Chromosome 5 Are Associated with Serum IgE Levels in Labrador Retrievers
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:6, s. e39176-
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Tidskriftsartikel (refereegranskat)abstract
- Crosslinking of immunoglobulin E antibodies (IgE) bound at the surface of mast cells and subsequent mediator release is considered the most important trigger for allergic reactions. Therefore, the genetic control of IgE levels is studied in the context of allergic diseases, such as asthma, atopic rhinitis, or atopic dermatitis (AD). We performed genome-wide association studies in 161 Labrador Retrievers with regard to total and allergen-specific immunoglobulin E (IgE) levels. We identified a genome-wide significant association on CFA 5 with the antigen-specific IgE responsiveness to Acarus siro. We detected a second genome-wide significant association with respect to the antigen-specific IgE responsiveness to Tyrophagus putrescentiae at a different locus on chromosome 5. A. siro and T. putrescentiae both belong to the family Acaridae and represent so-called storage or forage mites. These forage mites are discussed as major allergen sources in canine AD. No obvious candidate gene for the regulation of IgE levels is located under the two association signals. Therefore our studies offer a chance of identifying a novel mechanism controlling the host's IgE response.
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| 9. |
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| 10. |
- Tengvall, Katarina, 1980-, et al.
(författare)
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Bayesian model and selection signature analyses reveal risk factors for canine atopic dermatitis
- 2022
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Ingår i: Communications Biology. - : Springer Nature. - 2399-3642. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Canine atopic dermatitis is an inflammatory skin disease with clinical similarities to human atopic dermatitis. Several dog breeds are at increased risk for developing this disease but previous genetic associations are poorly defined. To identify additional genetic risk factors for canine atopic dermatitis, we here apply a Bayesian mixture model adapted for mapping complex traits and a cross-population extended haplotype test to search for disease-associated loci and selective sweeps in four dog breeds at risk for atopic dermatitis. We define 15 associated loci and eight candidate regions under selection by comparing cases with controls. One associated locus is syntenic to the major genetic risk locus (Filaggrin locus) in human atopic dermatitis. One selection signal in common type Labrador retriever cases positions across the TBC1D1 gene (body weight) and one signal of selection in working type German shepherd controls overlaps the LRP1B gene (brain), near the KYNU gene (psoriasis). In conclusion, we identify candidate genes, including genes belonging to the same biological pathways across multiple loci, with potential relevance to the pathogenesis of canine atopic dermatitis. The results show genetic similarities between dog and human atopic dermatitis, and future across-species genetic comparisons are hereby further motivated.
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