LUPA: A European initiative taking advantage of the canine genome architecture for unravelling complex disorders in both human and dogs

Lequarré, Anne-Sophie; Andersson, Leif; André, Catherine; Fredholm, Merete; Hitte, Christophe; Leeb, Tosso; Lohi, Hannes; Lindblad‐Toh, Kerstin; Georges, Michel

doi:10.1016/j.tvjl.2011.06.013

Cited by 99 publications

(94 citation statements)

References 34 publications

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“…The study was performed as part of the EU‐funded LUPA‐project,10 and was approved by an ethical committee in each participating country. Dogs were privately owned, and informed owner consent was obtained.…”

Section: Methodsmentioning

confidence: 99%

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Effect of Breed on Plasma Endothelin‐1 Concentration, Plasma Renin Activity, and Serum Cortisol Concentration in Healthy Dogs

Höglund

Lequarré

Ljungvall

et al. 2016

Veterinary Internal Medicne

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BackgroundThere are breed differences in several blood variables in healthy dogs.ObjectiveInvestigate breed variation in plasma endothelin‐1 (ET‐1) concentration, plasma renin activity, and serum cortisol concentration.AnimalsFive‐hundred and thirty‐one healthy dogs of 9 breeds examined at 5 centers (2–4 breeds/center).MethodsProspective observational study. Circulating concentrations of ET‐1 and cortisol, and renin activity, were measured using commercially available assays. Absence of organ‐related or systemic disease was ensured by thorough clinical investigations, including blood pressure measurement, echocardiography, ECG, blood and urine analysis.ResultsMedian ET‐1 concentration was 1.29 (interquartile range [IQR], 0.97–1.82) pg/mL, median cortisol concentration 46.0 (IQR, 29.0–80.8) nmol/L, and median renin activity 0.73 (IQR, 0.48–1.10) ng/mL/h in all dogs. Overall, breed differences were found in ET‐1 and cortisol concentrations, and renin activity (P < .0001 for all). Pair‐wise comparisons between breeds differed in 67% of comparisons for ET‐1, 22% for cortisol, and 19% for renin activity, respectively. Within centers, breed differences were found at 5/5 centers for ET‐1, 4/5 centers for cortisol, and 2/5 centers for renin activity. Newfoundlands had highest median ET‐1 concentration, 3 times higher than Cavalier King Charles Spaniels, Doberman Pinschers, and Dachshunds. Median renin activity was highest in Dachshunds, twice the median value in Newfoundlands and Boxers. Median cortisol concentration was highest in Finnish Lapphunds, almost 3 times higher than in Boxers.Conclusions and Clinical ImportanceBreed variation might be important to take into consideration when interpreting test results in clinical studies.

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Section: Methodsmentioning

confidence: 99%

“…In an European research project, LUPA, over 500 dogs of 9 breeds were examined at five centers looking for genetic determinants of variation in blood pressure, neuroendocrine, and metabolic variables 10. Simultaneously, breed differences in physiological variables were investigated.…”

mentioning

confidence: 99%

Effect of Breed on Plasma Endothelin‐1 Concentration, Plasma Renin Activity, and Serum Cortisol Concentration in Healthy Dogs

Höglund

Lequarré

Ljungvall

et al. 2016

Veterinary Internal Medicne

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“…Dogs were examined at 5 centers, as part of the EU‐funded LUPA project 33. Centers included University of Liège, Belgium; University of Copenhagen, Denmark; National Veterinary School of Alfort, France; University of Helsinki, Finland, and the Swedish University of Agricultural Sciences, Sweden.…”

Section: Methodsmentioning

confidence: 99%

Breed Differences in Natriuretic Peptides in Healthy Dogs

Sjöstrand

Wess

Ljungvall

et al. 2014

Veterinary Internal Medicne

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BackgroundMeasurement of plasma concentration of natriuretic peptides (NPs) is suggested to be of value in diagnosis of cardiac disease in dogs, but many factors other than cardiac status may influence their concentrations. Dog breed potentially is 1 such factor.ObjectiveTo investigate breed variation in plasma concentrations of pro‐atrial natriuretic peptide 31‐67 (proANP 31‐67) and N‐terminal B‐type natriuretic peptide (NT‐proBNP) in healthy dogs.Animals535 healthy, privately owned dogs of 9 breeds were examined at 5 centers as part of the European Union (EU) LUPA project.MethodsAbsence of cardiovascular disease or other clinically relevant organ‐related or systemic disease was ensured by thorough clinical investigation. Plasma concentrations of proANP 31‐67 and NT‐proBNP were measured by commercially available ELISA assays.ResultsOverall significant breed differences were found in proANP 31‐67 (P < .0001) and NT‐proBNP (P < .0001) concentrations. Pair‐wise comparisons between breeds differed in approximately 50% of comparisons for proANP 31‐67 as well as NT‐proBNP concentrations, both when including all centers and within each center. Interquartile range was large for many breeds, especially for NT‐proBNP. Among included breeds, Labrador Retrievers and Newfoundlands had highest median NT‐proBNP concentrations with concentrations 3 times as high as those of Dachshunds. German Shepherds and Cavalier King Charles Spaniels had the highest median proANP 31‐67 concentrations, twice the median concentration in Doberman Pinschers.Conclusions and Clinical ImportanceConsiderable interbreed variation in plasma NP concentrations was found in healthy dogs. Intrabreed variation was large in several breeds, especially for NT‐proBNP. Additional studies are needed to establish breed‐specific reference ranges.

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“…To overcome these limitations, the National Cancer Institute's Center for Cancer Research launched the Comparative Oncology Program, in 2003, to foster the use of naturally occurring cancer in pet animals as models of human cancer (10). A European initiative with a similar purpose-the LUPA project-has recently been launched (11).…”

Section: Introductionmentioning

confidence: 99%

CSPG4-Specific Immunity and Survival Prolongation in Dogs with Oral Malignant Melanoma Immunized with Human CSPG4 DNA

Riccardo¹,

Iussich

Maniscalco

et al. 2014

Clinical Cancer Research

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Purpose: Due to the many similarities with its human counterpart, canine malignant melanoma (cMM) is a valuable model in which to assess the efficacy of novel therapeutic strategies. The model is herein used to evaluate the immunogenicity, safety, and therapeutic efficacy of a human chondroitin sulfate proteoglycan-4 (hCSPG4) DNA-based vaccine. The fact that homology between hCSPG4 and cCSPG4 amino-acidic sequences stands at more than 80% provides the rationale for using an hCSPG4 DNA vaccine in the cMM model.Experimental Design: Dogs with stage II-III surgically resected CSPG4-positive oral MM were subjected to monthly intramuscular plasmid administration, which was followed immediately by electroporation (electrovaccination) for at least 6, and up to 20, months. The immunogenicity, safety, and therapeutic efficacy of the vaccine have been evaluated.Results: hCSPG4 electrovaccination caused no clinically relevant local or systemic side effects and resulted in significantly longer overall and disease-free survival times in 14 vaccinated dogs as compared with 13 nonvaccinated controls. All vaccinated dogs developed antibodies against both hCSPG4 and cCSPG4. Seven vaccinated dogs were also tested for a cCSPG4-specific T-cell response and only two gave a detectable interferon (IFN)g response.Conclusion: Xenogeneic electrovaccination against CSPG4 is able to overcome host unresponsiveness to the "self" antigen and seems to be effective in treating cMM, laying the foundation for its translation to a human clinical setting.

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LUPA: A European initiative taking advantage of the canine genome architecture for unravelling complex disorders in both human and dogs

Cited by 99 publications

References 34 publications

Effect of Breed on Plasma Endothelin‐1 Concentration, Plasma Renin Activity, and Serum Cortisol Concentration in Healthy Dogs

Effect of Breed on Plasma Endothelin‐1 Concentration, Plasma Renin Activity, and Serum Cortisol Concentration in Healthy Dogs

Breed Differences in Natriuretic Peptides in Healthy Dogs

CSPG4-Specific Immunity and Survival Prolongation in Dogs with Oral Malignant Melanoma Immunized with Human CSPG4 DNA

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