title: X-Linked Hereditary Nephropathy in Navasota Dogs: Clinical Pathology, Morphology, and Gene Expression During Disease Progression.
abstract: X-linked hereditary nephropathy (XLHN) in Navasota dogs is a spontaneously occurring disease caused by a mutation resulting in defective production of type IV collagen and juvenile-onset renal failure. The study was aimed at examining the evolution of renal damage and the expression of selected molecules potentially involved in the pathogenesis of XLHN. Clinical data and renal samples were obtained in 10 XLHN male dogs and 5 controls at 4 (T0), 6 (T1), and 9 (T2) months of age. Glomerular and tubulointerstitial lesions were scored by light microscopy, and the expression of 21 molecules was investigated by quantitative real-time polymerase chain reaction with selected proteins evaluated by immunohistochemistry. No significant histologic lesions or clinicopathologic abnormalities were identified in controls at any time-point. XLHN dogs had progressive proteinuria starting at T0. At T1, XLHN dogs had a mesangioproliferative glomerulopathy with glomerular loss, tubular necrosis, and interstitial fibrosis. At T2, glomerular and tubulointerstitial lesions were more severe, particularly glomerular loss, interstitial fibrosis, and inflammation. At T0, transforming growth factor β, connective tissue growth factor, and platelet-derived growth factor α mRNA were overexpressed in XLHN dogs compared with controls. Clusterin and TIMP1 transcripts were upregulated in later stages of the disease. Transforming growth factor β, connective tissue growth factor, and platelet-derived growth factor α should be considered as key players in the initial events of XHLN. Clusterin and TIMP1 appear to be more associated with the progression rather than initiation of tubulointerstitial damage in chronic renal disease.
authors.affiliation: Department of Comparative Biomedicine and Food Science, University of Padua, Viale dell'Università, Legnaro, Italy silvia.benali@alice.it.
authors.forename: S L
authors.initials: SL
authors.lastname: Benali
authors.affiliation: Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA.
authors.forename: G E
authors.initials: GE
authors.lastname: Lees
authors.affiliation: Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Nabity
authors.affiliation: Department of Comparative Biomedicine and Food Science, University of Padua, Viale dell'Università, Legnaro, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Aricò
authors.affiliation: Department of Animal Medicine, Production and Health, University of Padua, Viale dell'Università, Legnaro, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Drigo
authors.affiliation: Department of Comparative Biomedicine and Food Science, University of Padua, Viale dell'Università, Legnaro, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Gallo
authors.affiliation: Department of Comparative Biomedicine and Food Science, University of Padua, Viale dell'Università, Legnaro, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Giantin
authors.affiliation: Department of Comparative Biomedicine and Food Science, University of Padua, Viale dell'Università, Legnaro, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Aresu
mesh_terms: D000818:Animals; D024141:Collagen Type IV / Q000235:genetics; D018450:Disease Progression; D004283:Dog Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004285:Dogs; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D007150:Immunohistochemistry / Q000662:veterinary; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology; D008297:Male; D009394:Nephritis, Hereditary / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000662:veterinary*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011507:Proteinuria / Q000662:veterinary; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D024141:Collagen Type IV; D010982:Platelet-Derived Growth Factor; D016212:Transforming Growth Factor beta; C075278:platelet-derived growth factor A
keywords: Alport syndrome; TGFβ; TIMP1; clusterin; cystic glomerular atrophy; hereditary nephritis; juvenile glomerulonephropathy